33 Lethality of H1N1 Virus Drops to "Non-Epidemic Resting Levels" in Current Cycle; Virus' Infectivity Remains Increased (November 27, 2009)

32 New Non-Biological Synthetic Replikins™ Vaccines Shown to Be Effective and Fast (October 19, 2009)

31A New H1N1 Genomic Data Shows Decrease in Replikin Count* of Lethality Gene; Replikin Count of Infectivity Gene Remains High (September 30, 2009)

31 H1N1 Lethality Replikin Count Decreases, Infectivity Remains High (September 30, 2009)

30 Latest Replikins Data Predicts Continued High Level of H1N1 (Swine Flu) Infectivity and Lethality (July 28, 2009)

29 Lethality of H1N1 Influenza Virus Increasing According to Latest Replikins Analysis of Virus Peptide Genomic Data (June 10, 2009)

28 Swine Flu (H1N1) Infectivity to Increase Markedly and Lethality to Remain Low According to Latest Replikin* Peptide Genomic Data (May 23, 2009)

27 First H1N1 Swine Flu Vaccine, Replikins-Based, Is Ready Now For Testing Worldwide (May 4, 2009)

26 Replikins Provided Advance Warning of Mexican H1N1 "Swine Flu" Virus Outbreak (April 25, 2009)

25 Confirmation of Bogoch Replikins Influenza Patents By Harvard-CDC and Scripps-Crucell Data (March 20, 2009)

24 Rising H9N2 Influenza Replikin Count Has Doubled That of H5N1 (January 15, 2009)

23 Cancer Mortality Increases With Cancer Cell Replikin Count (December 4, 2008)

22 A new way to predict outbreaks: replikin peptide concentration in H5N1 influenza virus genome as a marker for lethal outbreaks (November 12, 2008)

21 H5N1 Virus Replikin Gene Counts Indicate a New More Virulent Influenza Cycle Has Begun (June, 27 2008)

20 Highest replikin concentrations and cyclical behavior related to human mortality are found in malaria trypanosomes (May 19, 2008)

19 Cycles of West Nile Virus replikin increases precede increases in the number of human cases (May 1, 2008)

18 H1N1 Influenza Virus with Highest Replikin Count™ Since the 1918 Pandemic Identified in the U.S. and Austria (April 7, 2008)

17 Replikins Oral Vaccine Synthesized in 7 days protects 91% of Shrimp Against Lethal Virus (March 11, 2008)

16 FluForecast® Replikin Count™ Predicts That The H5N1 Cycle Which Began In 1996 is Now Over (February 11, 2008)

15 Lethal Human H5N1 Influenza Virus Replikin Gene Still Upregulated (December 11, 2007)

14 AMAS Test Measures Lethal Replikin Gene Activity in Lung and Other Cancers (December 6, 2007)

13 Replikins, LLC Finds West Nile Virus Replikin Count™ Has Reached Its Highest Recorded Value (August 3, 2007)

12 Indonesia Reports Experiencing Human H5N1 Mortality Increase, as Predicted Last Year by Replikins' FluForecast® Quantitative Virus Analysis (June 8, 2007)

11 FluForecast® Trial in 2006 Predicted High Human H5N1 Mortality in Indonesia (May 9, 2007)

10 High Host Mortality Rate Quantitatively Related to High Virus Replikin Count (March 6, 2007)

9 Gene Segment Identified in Virulent Human H5N1 Viruses - Key Discovery May Enable Development of Vaccines, Therapeutics (January 25, 2007)

8 Human H5N1 Virus Replikin Count Overtakes Levels in H5N1 'Bird Flu' (December 27, 2006)

7 Rising H5N1 'Bird Flu' High-Virulence Sequences Found By Replikins, Ltd. (Nov 6, 2006)

6 Advance Warning Of H5N1 Influenza Outbreaks May Be Found In Shrimp Virus Reservoirs (Oct 26, 2006)

5 Replikins' FluForecast® Software Pinpoints Change in Deadly Bird Flu Amino Acid Sequence In Humans (June 3, 2006)

4 Replikins: Predicting global epidemics replication data (May 4, 2006)

3 Flu forecaster firm born (April 28, 2006)

2 Virus Replication Discovery Helps Predict Epidemics (April 24, 2006)

1 Replikins, Ltd. has discovered of a group of virus peptides that predict whether a virus is rapidly replicating and whether it is likely to spread (April 21, 2006)

33 Lethality of H1N1 Virus Drops to "Non-Epidemic Resting Levels" in Current Cycle; Virus' Infectivity Remains Increased (November 27, 2009)

Boston (PRWEB) November 27, 2009 -- Biotech firm Replikins Ltd., which has analyzed the H1N1 virus' genomic data from the 1918 pandemic through the prediction, outbreak, and progress of the current H1N1 pandemic, today issued its latest biochemical analysis of the virus. The new data shows that the lethality of the H1N1 ("Swine Flu") virus has dropped from its peak of 3.7 (s.d. 4.5) during the virus's current outbreak in the spring of 2009 to resting non-epidemic levels this week of 2.0 (s.d. 0.1). The H1N1 virus' infectivity count, however, remains increased.

The new data shows changes in the Replikin Count*, a measure of a virus's ability to rapidly replicate. A decrease in Replikin Count has signaled the end of each of the three influenza pandemics of the last century (H1N1, H2N2, and H3N2), the end of the SARS outbreak in 2003, and the end of the H5N1 (Avian Flu) outbreak in humans in 2008 (refs).

The company issued an interim advance report of this decrease in lethality on September 30, 2009 (refs). That report has now been confirmed by the current additional Replikins data and by the recent CDC epidemiological reports of declining total hospitalizations and deaths, and declining pediatric deaths from H1N1 (refs). In April 2008, Replikins issued a warning of an impending H1N1 influenza epidemic when the virus' Replikin Count reached levels not seen since the last H1N1 pandemic in 1918.

Without advance warning, the current biological methods of vaccine production cannot possibly meet the growing needs of a human population that today exceeds 6.7 billion. The current H1N1 Pandemic demonstrates the inherent limitations of biological vaccines, which simply do not permit the timely delivery of vaccine in sufficient quantities before a "hit-and-run" emergent viral disease like H1N1 has come and gone.

The best intentions and efforts of governments, pharmaceutical firms, and public health authorities cannot overcome the absence of advance warning, and the many months required from outbreak to delivery of the vaccine. It is becoming universally acknowledged that new vaccine technologies and methods for providing advance warning of viral outbreaks must be found.

At a meeting of the Influenza Congress USA in Washington, DC on November 19-20, 2009, Replikins chairman Dr. Samuel Bogoch presented new confirmatory evidence of two of its Replikins-based products that offer promise for advance warning of a viral outbreak and for the timely production and delivery of safe and effective vaccines. The first, called FluForecast®, is software that has correctly provided advance warning of two flu epidemics -- H5N1 (Avian Flu) and H1N1 (Swine Flu) -- by counting the increase in the number of Replikins in the virus' genes over time. For the current H1N1 pandemic, the company issued an advisory in April 2008 that forewarned its arrival one year later. With advance warning, scientists, public health officials and the pharmaceutical industry can develop, test and distribute the appropriate vaccine with enough time to avert the worst effects of emerging diseases.

Replikins Ltd. has successfully tested a second promising technology that allows for the faster development and deployment of safe and effective influenza vaccines. The company has now produced completely synthetic vaccines based on both new and conserved Replikin structures, which exclude all biological components and any contact with them. The process eliminates unwanted side effects from contaminants and the need for preservatives such as thimerosol. Synthetic Replikin vaccines made in seven days, given orally or intranasally, recently have been found independently to be effective in blocking emergent viruses including H5N1 in chickens, where it totally blocked virus excretion and thus potentially, virus reservoir formation (refs).

When asked at the Influenza Congress about the goals of Replikins Ltd., Dr. Bogoch replied: "Current biological vaccine technologies for emergent diseases are expected to provide, albeit 'too little and too late', approximately 125 million vaccine doses for people worldwide this fall (Klaus Stohr, Influenza Congress USA, Washington, DC, Nov.19-20, 2009). Replikins synthetic vaccines are targeting emergent diseases in the unserved global population of over six billion people, and selected animal populations, and FluForecast® can give advance warning of outbreaks.

"The company has announced the formation of WorldVaccines™ Ltd to test and distribute these new Replikins technologies, and invites all interested public health, pharmaceutical, financial, and other institutions to join it in testing and distributing FluForecast® and Replikins' synthetic vaccines against emerging diseases."

Contact: Samuel Bogoch, MD, PhD, (646) 320-5910, sbogoch@replikins.com

1. US Patent Office publications on Replikins 2002-2009;
2. BogochS, Bogoch,ES. Replikins: the Biochemistry of Rapid Replication, Begell House, New York, 2005;
3. Website Replikins Press 2006-2009;
4. CDC Weekly Reports website (google "FluView");
5. Betsy McKay, Wall Street Journal, page A3, November 21-22, 2009;
6. Jackwood, M. et al. Efficacy of a Replikin Peptide Vaccine Against Low Pathogenicity Avian Influenza H5 Virus. Avian Diseases, Publication Online, doi:10.1637/8892-042509-Res. Note.1; Hard copy Article In Press. July 2009.

32 New Non-Biological Synthetic Replikins™ Vaccines Shown to Be Effective and Fast; WorldVaccines™, Ltd. Formed for Testing and Distribution Old Biological Vaccines for Emergent Diseases - Too Little, Too Late (October 19, 2009)

BOSTON, Oct. 19 -- There is increasing evidence that, with best intent, current biological technology cannot supply the world's six billion humans, and animal populations, with vaccines against emerging diseases at a rate that can contend with a disease's rapid appearance and change, e.g., before the disease has come and gone. In view of Replikins Ltd.'s demonstration that Replikins™ chemically synthesized vaccines produced in seven days can be effective, the company today proposed these new vaccines as a solution to the problem of these emerging diseases. Furthermore, it established WorldVaccines™,Ltd to test and distribute synthetic Replikins™ vaccines.

As the first batches of the biological H1N1 ("Swine Flu") vaccines reach consumers worldwide, seven months after the flu outbreak, this small biotech firm in Boston today announced that it has created the first truly synthetic influenza vaccine that targets the broad range of A influenza viruses including H1N1, H5N1, H9N2, and H3N2, which was shown to be effective against the H5N1 (Avian Flu) virus. TransFlu™ is the first truly synthetic cross-strain pan-influenza vaccine.

In an independent study published in the peer-reviewed journal Avian Diseases, the synthetic Replikins TransFlu™ vaccine was shown to be effective in decreasing infectivity and completely blocking excretion of LPAI H5N1 virus in chickens, permitting for the first time the possibility of blocking animal virus reservoir development, a major precursor of human disease.

Both TransFlu™ and Taura Syndrome Virus vaccines were manufactured in seven days; kilogram amounts could be made in a few weeks, rather than six to 12 months needed for biological vaccine production. The cost to produce the synthetic vaccine is also far less than the cost of current biological production methods. Given the demonstrated effectiveness and rapid availability, it appears inevitable that synthetic Replikins™ vaccines will eventually replace biological vaccines.

Further, until now, all influenza vaccines have been produced in biologically living cells. Whether whole virus or recombinant virus sections are reproduced in eggs, kidney, hamster, E.coli, or other cells, these living cells provide the obligatory contamination in the vaccine of thousands of unwanted immunogenic proteins, the potential for other virus contamination (viruses only reproduce in living cells), and the need for potentially toxic preservatives.

Over the last decade, Drs. Samuel and Elenore Bogoch have been developing vaccine-manufacturing methods that are non-biological, based on software algorithms designed to study virus structure, and organic chemistry. The new, completely synthetic Replikins™ Vaccine Technology (1-4) targets a group of genomic peptides that they discovered and named Replikins™. These genomic peptides were found to be conserved in viruses cross-strain over decades, and to be related to rapid replication and epidemic outbreaks.

The centrality of the Replikins™ to influenza has been confirmed recently by the data of two independent groups, Harvard-CDC and Scripps-Crucell. Their findings demonstrate that inhibitory antibody lands on and binds selectively to the very peptides that the Drs. Bogoch have previously identified as Replikins™.

Three months to one year in advance of an outbreak, the related Replikins™ FluForecast® software warns of the oncoming emergent disease. This technology was recently validated when it successfully identified, a year in advance, the current H1N1 outbreak. The technology also defines the Replikins™ that need to be synthesized in the vaccine. Thus the Replikins™ structures, which make up both the newly discovered infectivity and lethality genes within the virus genome, provide the keys to both advance warning and synthetic vaccine production.

1. Replikins.com. Replikins Press. 31 reports published by Replikins Ltd.
2. Bogoch, S. and Bogoch, E.S., Replikins: the Chemistry of Rapid Replication. Monograph. Begell House, New York, 2005.
3. Bogoch, S. et al., Replikins. Published patent applications and issued patents, US Patent Office, 2002-2009.
4. Jackwood, M. et al. Efficacy of a Replikin Peptide Vaccine Against Low Pathogenicity Avian Influenza H5 Virus. Avian Diseases, Publication Online, doi:10.1637/8892-042509-Res. Note.1; Hard copy Article In Press. July 2009.

31A New H1N1 Genomic Data Shows Decrease in Replikin Count* of Lethality Gene; Replikin Count of Infectivity Gene Remains High (September 30, 2009)

Reported Incidence of Worldwide and Pediatric Deaths Correlate with H1N1 Virus Lethality Gene Replikin Count

Possibility of H1N1-H5N1 Combination: Replikins TransFlu™ Vaccine Against It

BOSTON, Sept. 30 -- The latest H1N1 genomic data shows a 50% drop in the Replikin Count™ of the virus's replikins lethality gene since its recorded highs in April 2009. In contrast, the Replikin Count of the virus's infectivity gene showed a continued elevation. The Boston-based biotech firm Replikins Ltd. (www.replikins.com) today released the new quantitative virus data collected by the same FluForecast® software which correctly predicted the current outbreak of H1N1 in April 2008, a year before the outbreak occurred.

"In spite of the drop in the Replikin Count of the H1N1 lethality gene, followed by a drop in mortality rate worldwide, the Count remains 20% elevated compared to its resting levels between 1934 and 2008. This means there are still rapidly replicating individual viruses within the currently circulating H1N1 virus population that contain high Replikin Counts in their lethality genes. In previous virus outbreaks these high counts were associated with high mortality. With the persistent high infectivity, the risk of serious disease therefore remains," explained Samuel Bogoch, MD PhD, chairman of Replikins Ltd. The FluForecast® virus structural data typically provides a three-month to one-year prediction of the course of the clinical manifestations of the viral outbreak.

In the CDC Weekly reports, weeks 36 and 37, ending September 12th and 19th, 2009, the number of influenza-associated pediatric deaths, which peaked in June, 2009 following the peak Replikin Count of the Lethality Gene of April, 2009, have now decreased following the decrease in the Count. The number of pediatric deaths thus followed the rise and fall of the Replikin Count of the Lethality Gene (Figure).

In contrast, with noteworthy reproducibility of the method, as of September 29, 2009, the Infectivity Gene Count has remained elevated, decreasing only 3% in its mean since its high in April 2009, thus giving no significant sign of an abatement, as compared to SARS when a sharp drop in the Replikin Count of the spike protein in the year of the outbreak, 2003, signaled the abrupt end of the clinical outbreak.

Possible H5N1 - H1N1 combination
As in H1N1, the replikins in H5N1 ("Bird Flu") were found not to be distributed evenly throughout the genome but to be concentrated in the same two areas as in H1N1, and associated with lethality and infectivity. Clinically, H1N1 has high infectivity and low lethality, the opposite of H5N1, which has low infectivity and high lethality; and the Replikin Counts correspond exactly to the clinical characteristics of each strain. H5N1 lethality in humans has reached 80% in recent outbreaks.

Because of the known ability of segments of the genomic sequences to transfer between influenza strains, the possibility that the high infectivity of H1N1 might be combined with the high lethality of H5N1 is of concern, and it appears that there is no method available to predict the probability of this occurrence.

Replikins TransFlu™ Vaccine
To prepare in advance for the possibility of an H1N1-H5N1 combination occurring, a synthetic replikin vaccine named Replikins TransFlu™ has been developed by Replikins, Ltd. This vaccine is based on identical replikin structures shared in the common A Influenza strains, H1N1, H5N1, H9N2, and H3N2, TransFlu Vaccine testing has begun, and the vaccine is available to institutions worldwide for further testing. A recent blind test at the University of Georgia of replikins TransFluTM vaccine was successful against H5N1 in chickens (see below). and tests against H1N1 and H5N2 are following. Consumption of virus excretions by neighboring chickens is a major mechanism by which influenza reservoirs are maintained both in Asia and North America; this constant transfer could not be blocked by previous massive vaccine efforts in China.

In the recent peer-reviewed publication by Jackwood et al (Avian Diseases, Publication Online: doi: 10.1637/8892-042509-ResNote.1), synthetic Replikins TransFluTM vaccine, produced in 7 days, was shown to be effective in decreasing infectivity and completely blocking excretion of LPAI H5N1 in chickens.

The publication concludes: "Taken together, these data indicate that a replikin peptide vaccine specifically made against the H5N1 Black Duck/NC/674-964/06 and administered 3 times to the upper-respiratory tract, was capable of protecting chickens from infection and shedding of the homologous virus, which is extremely important because reduced virus shedding and transmission decreases the potential for H5 LPAI viruses to become HPAI viruses. The study is also important because it shows that the vaccine can be effectively mass delivered to the upper-respiratory tract."

About Replikins Ltd. and LLC (www.replikins.com)
BVI and Boston-based biotech companies develop and market novel forecasting tools and synthetic vaccines to fight virulent rapidly replicating diseases including bird flu, swine flu, malaria, and HIV. The companies' predictive products and vaccines in development are based upon the companies' discovery of Replikins, a new group of genomic peptides related to the rapid replication function in viral and other diseases. (Replikin Count™ = number of replikins per 100 amino acids). The company has designed unique products to predict the emergence of virulent strains of particular diseases (FluForecast™) and is designing synthetic vaccines specifically tailored to combat a given strain and against shared properties of several strains (Syntope™ and TransFlu™ vaccines). The companies are partnering with governments and the private sector in providing predictive tools and vaccines in furtherance of the public health initiative to prevent and combat epidemics.

31 H1N1 Lethality Replikin Count Decreases, Infectivity Remains High; (September 30, 2009)

Synthetic Replikins H1-H3-H5 Trans-Flu™ Vaccine Found Effective

Boston, September 30, 2009.

Figure. Virus Structure Predicted Outbreak and Course of H1N1 2009 Pandemic

Replikins, Ltd. published a warning on April 7, 2008 (1#18), one year before the current outbreak, that as determined by FluForecast® software, the concentration of a group of genomic peptides in the H1N1 influenza virus in humans, replikins (2), which was increasing since 2001, had reached the level of 7 per 100 amino acids, (Figure, red), a concentration which had occurred previously in the H1N1 pandemic of 1918. In the first three months of 2009, H1N1 outbreaks were reported in Mexico and California, then expanded globally into the present H1N1 pandemic. Since April 2009, FluForecast® software methods have provided advance information on the changing virus structure as it predicts the clinical course of the H1N1 pandemic (Figure).

All data published on PubMed was analyzed for replikin concentration in the virus genomes from 1918 to the present worldwide. The number of specimens from which sequence data for the hemagglutinin and polymerase genomic areas could be obtained for analysis from 2001 through 2008 was 855; in 2009 alone to date, 1,561.

The expectation of a summer interruption in the pandemic was contradicted by the prediction of FluForecast® data in May 2009 (1#28); and infections proceeded throughout the summer in the UK, China, the U.S.., and many other Northern Hemisphere countries, where they were not expected, as well as in the Southern Hemisphere where they were. As expected, the peak Replikin Count, between December 2008 and April 2009, was followed two months later in June in the U.S. by the peak of H1N1 pediatric deaths (3). Before the discovery of the replikins, to our knowledge, no virus structure had been reported which quantitatively correlated with or predicted virus outbreaks or clinical course.

Replikins were found not to be distributed evenly throughout the genome but to be concentrated in two areas: one associated with lethality (in the polymerase area) and one with infectivity (in the hemagglutinin area).

The Figure shows that for the H1N1 Infectivity Gene (red), the Mean Replikin Count increased from 4.3 (+/-2) in 2001 to 6.7 (+/-1.2) in 2008 (p<.001), when the warning was published, and increased another 43% to 10 by April 2009, when the clinical H1N1 outbreak was reported. In June 2009, WHO stated that the outbreak had spread globally sufficiently to be declared a pandemic. As of September 2009 the Infectivity Gene Count has remained elevated, decreasing only 3% in its mean since the high in April, 2009, thus giving no significant sign as yet of an abatement, as occurred in SARS when a sharp drop in the Replikin Count of the spike protein in the year of the outbreak, 2003, signalled the abrupt end of the clinical outbreak.

The Figure also shows that for the H1N1 Lethality Gene (black), the Mean Replikin Count between 2001 to 2008, despite some activity, did not increase significantly as did the Infectivity Gene. However, the Standard Deviation of the Mean (SD), which is indicative that some viruses in the population have high Replikin Counts and are engaging in high replication rates, increased 5-fold between 2001 and December 2008, then between December 2008 and April 2009 the SD increased 45-fold over that of 2001. It has gradually decreased by 50% from its high in April 2009 to that on September 21, 2009 (p<.001)*(Figure). However, the mean Count is still 20% elevated, and the standard deviation of the mean, is still 25 times greater than the 'resting' level of 2001. This indicates that there are still active individual viruses within the currently circulating H1N1 virus population which contain increased Replikin Counts in their Lethality Genes, suggesting deaths are still possible. The overall trend, however, since April 2009, as seen in the Figure is clearly towards a return to the lower 'resting' Lethality Replikin Count of 2, which predominated from 1980 to 2008, or less than 2 which predominated from 1934 to 1979; these low Counts were generally accompanied by low clinical H1N1 lethality from 1934 to 2008. The increase in the Count of the Replikins in April 2009, together with the current statistically significant decline in the Lethality Gene Count, which was followed by the drop in H1N1 influenza-associated pediatric mortality since June 2009 (3), gain in significance against the background of low H1N1 Counts and low H1N1 influenza mortality from 1934 to 2008. Although high H1N1 infectivity is predicted to persist, there is no indication from the present data that a mortality rate even as high as that in April 2009 is to be anticipated. However, with the persistent high infectivity, the risk of serious disease remains.

New H5N1 Cycle Signaled by H9N2 Replikin Count Increase; Possible H5N1 - H1N1 Combination

As in H1N1, the replikins in H5N1 were found not to be distributed evenly throughout the genome but to be concentrated in the same two areas as in H1N1, and associated with lethality and infectivity. Clinically, H1N1 has high infectivity and low lethality, the opposite of H5N1, which has low infectivity and high lethality. Between 2004 and 2008, the Replikin Count of the H5N1 Infectivity Gene in birds has remained at approximately 5, whereas the mean Count of the Lethality Gene has risen more than seven-fold, from 2+/-0.1 in 2004 to 15.1+/-6.5 in 2008, and to as high as 30.0 in the precursor of H5N1, H9N2, in chickens(1#24). The integrity and independence of infectivity and lethality genes is thus established by their opposite activities, in one host, humans, as seen in the Figure, and in two different hosts, humans vs. birds (the test of 'Double Discrimination').

A proof of principle that it is possible to quantify the lethality of a virus by counting the number of replikins per 100 amino acids in the virus genome is supported in the present results. This proof of principle was first achieved in a blind predictive study of the relative lethality of four strains of Taura Syndrome virus (1#10). The applicability of this principle then was realized when this virus was blocked by a Syndrome virus specific synthetic replikins vaccine, protecting shrimp 91% from lethality (1#17). In another example, an increase in the lethality of H5N1 in human cases in 2007-08 was predicted in advance by the strain-specific Replikin Count of the Lethality Gene of H5N1 (1#11). Similarly, by comparing the Replikin Counts of the Lethality Genes of H5N1 Genes in eight Asian countries in 2006, the geographic site which would be first and worst struck in 2007 was correctly predicted as Indonesia (1#11,12).

The independent function of the Replikin Lethality and Infectivity genes demonstrated by the H1N1 quantitative Replikin Count may explain the surprise expressed by some that the mortality rate has not increased, and according to the latest replikins data, may be expected to decrease further.

Because of the known ability of segments of the genomic sequences to transfer between influenza strains, the possibility that the high infectivity of H1N1 might be combined with the high lethality of H5N1 is of concern, and there is apparently no method available to predict the probability of this occurence.

Replikins TransFlu™ Vaccine

To prepare in advance for the possibility of an H1N1-H5N1 combination occurring, a synthetic replikins vaccine named Replikins TransFlu™ , because it is based on shared replikins structures in the common A Influenza strains, has been developed by Replikins, Ltd. The synthetic TransFlu™ Vaccine is based on replikins found to be structurally shared between H1N1, H5N1, H9N2, and H3N2.

Trans-Flu Vaccine testing has begun, and the vaccine is available for further testing. A recent test by Jackwood et al at the University of Georgia of replikins TransFlu™ vaccine was successful against H5N1 in chickens (see below); and tests against H1N1 and H5N2 are following. Consumption of virus excretions by neighboring chickens is a major mechanism by which influenza reservoirs are maintained both in Asia and North America; this constant transfer could not be blocked by previous massive vaccine efforts in China. In the recent peer-reviewed publication (4), synthetic Replikins TransFlu™ vaccine, produced in 7 days, was shown to be effective in decreasing infectivity and completely blocking excretion of LPAI H5N1 in chickens. The publication concludes: "Taken together, these data indicate that a replikin peptide vaccine specifically made against the H5N1 Black Duck/NC/674-964/06 and administered 3 times to the upper-respiratory tract, was capable of protecting chickens from infection and shedding of the homologous virus, which is extremely important because reduced virus shedding and transmission decreases the potential for H5 LPAI viruses to become HPAI viruses. The study is also important because it shows that the vaccine can be effectively mass delivered to the upper-respiratory tract."

In defending against rapidly emerging and changing infectious diseases, the possibility has thus been introduced that many or all vaccines will be produced timely in the future by organic chemical synthesis, with the goal of avoiding both the 'too little, too late' syndrome, evident in vaccine production for the current H1N1 pandemic, and the side effects of biological vaccines.

Notes

* Dates in the Figure are PubMed publication dates, which are from one to four months after the dates the specimens were actually collected. The time difference represents the time taken for sequence analysis, review and publication. 'Real-time' replikin analysis of the specimens could more accurately be realized if it is found possible in the future to shorten the time for sequence analysis and publication.
** In 1976, a localized H1N1 outbreak led to the administration of millions of doses of vaccine because of the fear that a second H1N1 pandemic was beginning (5). Analysis of the recorded H1N1 virus genomic sequences of 1976 showed that the Replikin Count of the Lethality Gene was only 1.9+/-0. If this information about the H1N1 virus structure had been known in 1976 might it have influenced the reaction to the outbreak?

1. Replikins Ltd. Website : Replikins report numbers (#1-30).
2. Bogoch,S. Bogoch,ES. Replikins: the Biochemistry of Rapid Replication. Monograph, Begell House, New York. 2005.
3. CDC FluView, Week 36 and 37, ending September 12th and 19th, 2009.
4. Jackwood, et al. Efficacy of a Replikin Peptide Vaccine Against Low Pathogenicity Avian Influenza H5 Virus. Avian Diseases, Publication Online: doi: 10.1637/8892-042509-ResNote.1; Hard copy Article In Press. July 2009.
5. Sencer, DJ, Miller,JD. Emerging Infectious Diseases. www.cdc.gov/eid. Vol 12, No. 1, January 2006.

For subscriptions to weekly or daily FluForecast® reports
contact JMckenney@Replikins.com

30 Latest Replikins Data Predicts Continued High Level of H1N1 (Swine Flu) Infectivity and Lethality(July 28, 2009)

FluForecast® Analysis of June and July 2009 Genomic Data Shows No Sign of Virus Easing Over Next 6 to 12 Months

BOSTON, July 28, 2009 - Biotech firm Replikins Ltd. (www.replikins.com) today released its analysis of the June and July genomic data that predicts the rates of infectivity and lethality of the H1N1 (Swine Flu) virus. The quantitative analysis shows continued elevated levels in the Replikin Counts* of both Infectivity and Lethality genes, which indicate that the end of the current outbreak is not yet in sight.

"The H1N1 virus continues to be increased in its lethality and infectivity according to our most recent data," explained Samuel Bogoch MD PhD, chairman of Replikins Ltd. "Compared to the SARS outbreak in 2003, where that virus's Replikin Count rapidly decreased shortly after the outbreak, followed swiftly by clinical abatement, the Swine Flu does not show any sign of easing off."

The current H1N1 outbreak in early 2009 was predicted by the company's FluForecast® software in April 2008, when the Replikin Count reached 7 -- the same level achieved during the H1N1 1918 Pandemic. (See Figure). While most expected a summer pause, the Replikins Infectivity Gene data published in late May 2009 indicated that no respite was to be expected. Since then, the global spread of the virus has been so rapid that both the WHO and the CDC last week announced they have stopped counting cases.

Specifically, the Replikin Count of the H1N1 Infectivity Gene, doubled from 2002 to 2008, increased an additional 43% in the first few months of 2009, and maintained that elevated level from May into July, while the Lethality Replikin Count, up 65% from May to June, remains elevated in July but at a slightly lower level -- still 40% above that of May. Changes in Replikin Count have been shown to precede the clinical reality by six to 12 months in all other influenza outbreaks of record.

FluForecast® is the first data-driven service to assess the risks posed by all strains of influenza virus wherever genome sequence data is available. It demonstrated that all influenza pandemics and epidemics, and their cessation, over the last 90 years have been associated with statistically significant changes in the concentration (Replikin Count) of a particular group of genomic peptides of the virus associated with rapid replication (Replikins). It is the first and only such quantitative correlation of influenza epidemics with a virus's structure.

"The technology now exists to tackle one of the most vexing problems facing virologists and public health officials: how to correctly predict if, when, and where a particular strain of influenza virus will break out," added Dr. Bogoch. "We now have proprietary software that can analyze vast quantities of publicly available genomic data, specifically for the dynamics of rapid replication, which has led to the development of this new and unique tool for predicting these global health threats. Advance strain-specific warning permits time to respond with public health containment measures and for the development of 'tailor-made' vaccines."

This month, Replikins, Ltd. was contacted by and reached out to senior government health officials in dozens of countries to offer the FluForecast® service. Many plan to introduce the service to their public health surveillance programs both for early warning and for tracking epidemics.

About Replikins Ltd.
Replikins, LLC. (www.replikins.com), a Boston-based biotech company, and Replikins, Ltd., develop and market novel forecasting tools and synthetic vaccines to fight virulent rapidly replicating diseases including bird flu, malaria, and HIV. The company's predictive products and vaccines in development are based upon the company's discovery of Replikins, a new group of peptides related to the rapid replication function in viral and other diseases. The company has designed unique products to predict the emergence of virulent strains of particular diseases (FluForecast®) and is designing synthetic vaccines specifically tailored to combat a given strain and against shared properties of several strains (Syntope™ vaccines). The company is partnering with governments and the private sector in providing predictive tools and vaccines in furtherance of the public health initiative to prevent and combat epidemics.

* Replikin Count™ -- Number of Replikins per 100 amino acids. Within the last century there have been three influenza pandemics, each strain specific: H1N1 in 1918; H2N2 in 1957; and H3N2 in 1968. The company's research team analyzed the amino acid sequences of the reported strains and found that with each pandemic there was a strain-specific increase in the Replikin Count™ peptide quantities within the strain, followed by a decrease in Replikin Count™ peptide quantities and several years later a rebound increase associated in each case with a strain-specific rebound epidemic.
Contact: John McKenney
Replikins Ltd.
jmckenney@replikins.com
617-536-0220

29 Lethality of H1N1 Influenza Virus Increasing According to Latest Replikins Analysis of Virus Peptide Genomic Data (June 10, 2009)

Boston Biotech Firm Reports First Rise in 76 Years of Replikin Count* of H1N1 Lethality Gene

BOSTON, June 10, 2009 - An analysis of the latest peptide genomic data for the H1N1 influenza virus indicates that the current global outbreak of H1N1 is increasing in its capacity for lethality. The new sequence data on PubMed of the past two weeks through June 10, 2009 showed an increase in the Replikin Count* of the Replikin Lethality Gene in the pB1 genomic area from a mean of 2±0.2 in 2008 to a mean of 3.2±3.7 in 2009 (p<0.001). The Replikin Count of the Lethality Gene in 836 previous H1N1 influenza virus isolates has remained essentially unchanged (at 2) since 1933.

These analyses were conducted by the Boston-based biotech firm Replikins, Ltd. (www.replikins.com) using its FluForecast® software. A year ago (4/7/08), using the same software, the firm predicted the current H1N1 virus outbreak, and last month (5/23/09) an increase in the Replikin Count of the Replikin Infectivity Gene in the hemagglutinin area indicated a marked increase in infectivity of the evolving H1N1 virus. "Last month the H1N1 genomic data indicated some bad and some good news. While it indicated an increase in the infectivity of the H1N1 virus, its lethality appeared to remain relatively low," noted Sam Bogoch MD PhD, chairman of Replikins Ltd. "However, the FluForecast® analysis of new data of the past few weeks, through June 10th, on 144 new specimens published on PubMed, indicate an increase in the current H1N1 outbreak's capacity for lethality. Since the software also permitted the automated analysis of all sequence data available on PubMed for all previous years, it was noted that this is the first such significant increase in the Replikin Count of the H1N1 Lethality Gene in 76 years. This is cause for concern and an accelerated vaccine effort."

For both the Infectivity Gene and the Lethality Gene, a significant increase in Replikin Count has invariably been followed by an increase in infectivity or lethality in influenza. While both the Replikin Infectivity Gene and the Replikin Lethality Gene have been found to act independently in all common influenza strains in human, swine, and bird hosts, both of these genes have been inhibited by the Two-Punch™ vaccine system-designed to be concurrently directed at both genes.

The company recently announced that it has made available for testing against H1N1 a Two-Punch™ PanFlu™ vaccine. The same vaccine system has been successfully tested against H5N1 in chickens.

About Replikins Ltd.
Replikins, LLC. (www.replikins.com), a Boston-based biotech company, and Replikins,Ltd., develop and market novel forecasting tools and synthetic vaccines to fight virulent rapidly replicating diseases including bird flu, malaria, and HIV. The company's predictive products and vaccines in development are based upon the company's discovery of Replikins, a new group of peptides related to the rapid replication function in viral and other diseases. The company has designed unique products to predict the emergence of virulent strains of particular diseases(FluForecast™) and is designing synthetic vaccines specifically tailored to combat a given strain and against shared properties of several strains (Syntope™ vaccines). The company is partnering with governments and the private sector in providing predictive tools and vaccines in furtherance of the public health initiative to prevent and combat epidemics.

* The company's vaccines and predictive tools are based on the company's discovery of a new group of peptides related to rapid replication called Replikins, whose increase in concentration in virus or other organism proteins (Replikin Count™ = number of replikins per 100 amino acids) is associated with rapid replication.

28 Swine Flu (H1N1) Infectivity to Increase Markedly and Lethality to Remain Low According to Latest Replikin* Peptide Genomic Data (May 23, 2009)

Boston-based biotech firm Replikins Ltd. (www.replikins.com) last week analyzed the most recent peptide genomic sequence data available and determined that the infectivity of the H1N1 virus will increase markedly, while its lethality will remain relatively low for the immediate future. The company's quantitative analysis of the most recent sequence data available on PubMed, a standard scientific repository for published papers, showed an increase of 46% in the Replikin Count* over the past five months.

Boston, MA (PRWEB) May 23, 2009 -- Amid all the speculation over what course the Swine Flu epidemic will take, Boston-based biotech firm Replikins Ltd. (www.replikins.com) last week analyzed the most recent peptide genomic sequence data available and determined that the infectivity of the H1N1 virus will increase markedly, while its lethality will remain relatively low for the immediate future.

The company's quantitative analysis of the most recent sequence data available on PubMed, a standard scientific repository for published papers, showed an increase of 46% in the Replikin Count* over the past five months. This points to a marked increase in infectivity in humans. At the same time, while the total number of replikins has gone up significantly, their composition appears to have changed in a way that makes them more closely resemble their counterparts in earlier pandemics.

The firm, which had predicted a year ago the likelihood of the current H1N1 outbreak, used its proprietary FluForecast™ software program to make these determinations. "The dual differentiation of these properties may provide advance warning of the future course of H1N1," noted Samuel Bogoch MD PhD, chairman and founder of Replikins Ltd. "Our understanding of the protein chemistry of rapid replication enables us to develop synthetic vaccines specifically tailored to destroy or restrict replication of the targeted virus strains prior to an outbreak."

Earlier this month, Replikins announced that it had succeeded in synthesizing the first H1N1 influenza vaccine, which is now ready for testing. It used the same approach to produce a peptide H5N1 (avian flu) vaccine that successfully blocked low path H5N1. It has not previously been possible to correlate virus structures with a virus outbreak or cessation of outbreak, let alone to predict six to 12 months ahead of the outbreak or its cessation. In 2001, Drs. Samuel and Elenore Bogoch first demonstrated this correlation retrospectively for whole-organism replikin counts in outbreaks and pandemics of the common influenza strains over the past century.

About Replikins Ltd.
Replikins, Ltd. (www.replikins.com), a Boston-based biotech company, develops and markets novel forecasting tools and synthetic vaccines to fight virulent rapidly replicating diseases including bird flu, malaria, and HIV. The company's predictive products and vaccines in development are based upon the company's discovery of Replikins, a new group of peptides related to the rapid replication function in viral and other diseases. The company has designed unique products to predict the emergence of virulent strains of particular diseases (FluForecast™) and is designing synthetic vaccines specifically tailored to combat a given strain and against shared properties of several strains (Syntope™ vaccines). The company is partnering with governments and the private sector in providing predictive tools and vaccines in furtherance of the public health initiative to prevent and combat epidemics.

The company's vaccines and predictive tools are based on the company's discovery of a new group of peptides related to rapid replication called Replikins, whose increase in concentration in virus or other organism proteins (Replikin Count™ = number of replikins per 100 amino acids) is associated with rapid replication.

27 First H1N1 Swine Flu Vaccine, Replikins-Based, Is Ready Now For Testing Worldwide (May 4, 2009)

London, U.K. May 4, 2009. A synthetic peptide H1N1 vaccine is available now for testing worldwide, from Replikins Ltd. The company has developed the vaccine based on the same Replikins peptide technology which provided the surprise advance warning one year ago that the current H1N1 outbreak/pandemic was on its way (replikins.com). A unique advantage of the Replikins vaccine is its rapid availability; the WHO, CDC and others have stated that conventionally-developed H1N1 vaccines will not be ready for many months. This key advantage is based on the company's ability to swiftly identify, and make molecular vaccines based on, key sub-sequences of the virus genome that are critical to its rapid replication. In contrast with the decades-old production techniques used for most vaccines, the company also takes full advantage of modern peptide synthesis techniques to allow rapid production of its vaccines.

In April 2008, Replikins, Ltd announced the likelihood of H1N1 outbreaks based on the company's patented Replikin Count™ genomics technology, which examines specific regions in virus genes that have been linked with past epidemics. The company's chairman, Dr. Samuel Bogoch, found that some of these regions have been conserved for decades. In H1N1 last year the company detected the highest concentrations of these specific regions ever seen, except for those from the 1918 flu pandemic which killed tens of millions of people. To date, no other method has been able to predict whether and what strain of a given organism will threaten a human or animal population.

The same proprietary technology, based on genomic Replikin Count™, which permitted one year advance warning that H5N1 with higher human lethality would strike in 2007, and that H1N1 would strike this year, has been used to manufacture synthetic conserved replikin vaccines against both these influenza strains, Replikins H5N1 Bird Flu Vaccine™ and Replikins H1N1 Swine Flu Vaccine™, as well as a Replikins PanFlu Vaccine™.

The company is producing the new H1N1 vaccine product after achieving independent test results of the safety and efficacy of its synthetic vaccines against two viruses in two different host populations: the lethal Taura virus in shrimp populations, and the avian flu (H5N1) in chicken populations. The company's closely related Replikins vaccine against H5N1 avian flu, produced in a 7 day period, was recently tested at the University of Georgia and shown to block H5N1 virus entry, replication, and excretion in chickens (paper submitted for publication).

Institutions requesting Replikins' H1N1 vaccine for testing should contact: jmckenney@replikins.com

26 Replikins Provided Advance Warning of Mexican H1N1 "Swine Flu" Virus Outbreak (April 25, 2009)

April 25, 2009 -- Replikins, Ltd. published a FluForecast® warning in April 7th, 2008, a year before the recent Mexico and California H1N1 cases. The company was able to state the likelihood of H1N1 outbreaks based on its patented Replikin Count™ genomics technology, which examines specific regions in virus genes which have been linked with past epidemics.

The April 2008 announcement, attached below as published on the Web, stated that in H1N1 the company had then detected the highest concentrations of these specific regions ever seen, except for those from the 1918 pandemic which killed millions of people. Today, the company is actively pursuing licensing partnerships to apply its groundbreaking technology not only to early warning systems, but also to the development of synthetic vaccines to prevent or slow future epidemics.

Replikins, Ltd. published a FluForecast® warning on April 7th, 2008, a year before the recent Mexico and California H1N1 cases. The company was able to state the likelihood of H1N1 outbreaks based on its patented Replikin Count™ genomics technology, which examines specific regions in virus genes which have been linked with past epidemics.

A synthetic H1N1 Replikins Vaccine is available for testing. A similar synthetic Replikin Vaccine has been shown to successfully block the entry of H5N1 virus into, replication in, and excretion from chickens. Another synthetic Replikin Vaccine has been shown to protect 91% of shrimp from the lethal Taura Syndrome Virus. The company is able to produce these vaccines in as little as 7 days, rather than the many months needed for traditional vaccines, because they are synthesized at the peptide level.

25 Confirmation of Bogoch Replikins Influenza Patents By Harvard-CDC and Scripps-Crucell Data (March 20, 2009)

Boston, March 20, 2009. Replikins, Ltd. announced today that data recently published from Harvard-CDC and Scripps-Crucell in Nature1 and Science2 confirms the 2001 discoveries by Dr. Samuel and Elenore Bogoch of peptides in the hemagglutinin unit of influenza, which they named Replikins, which are shared across flu strains, conserved over time, associated with the last three pandemics of 1918, 1957 and 1968, as well as current H5N1 outbreaks, and are the basis of broad spectrum flu vaccines. The Replikins sequences, as specified by the Bogoches, are the subject of granted patents from 2001 and a 2005 monograph3.

The amino acid contact points between the neutralizing antibody and the virus that the Harvard-CDC and Scripps-Crucell investigators both observed, out of over 500 possible sites, are in the influenza Replikins. The confirming groups' data also verified the Bogoch 2001 findings of conservation of these very Replikins peptides over decades, and the sharing of Replikins between strains of influenza, making general flu vaccines possible for the first time.

The Replikins peptides, associated with rapid replication, are quantitatively trackable and predictive of the intensity, timing, and country of outbreak. The company's FluForecast® software has correctly predicted recent H5N1 outbreaks and the countries in which they were going to occur.4

Replikins, which are quantitatively related to lethality in influenza and other infectious diseases, such as HIV, anthrax, and malaria, as well as cancer, and a range of animal diseases, are the subject of synthetic vaccines in development at the Company.

1. Sui, J. et al. "Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses.", Nature Structural and Molecular Biology, published online:22 February,2009, doi:10.1038-nsmb.1566.

2. Ekeirt, D.C. et al, "Antibody Recognition of a Highly Conserved Influenza Virus Epitope", Science DOI: 10.1126-science.1171491, Science Published online, Feb. 26 2009

3. Bogoch S. and Bogoch, E.S. Replikins, the Chemistry of Rapid Replication. With examples in influenza, HIV, AIDS, SARS, Malaria, and Cancer. Begell House,Inc. New York, Wallingford, U.K. ISBN 1-56700-200-5, 2005.

4. On-line: see 'Replikins Press', 2006 - 2008. (Press release #12 Indonesia Reports Experiencing Human H5N1 Mortality Increase, as Predicted Last Year by Replikins' FluForecast® Quantitative Virus Analysis (June 8, 2007)

REPLIKINS, Ltd. 38 the Fenway, Boston, MA 02215.
Contact: jjosephson@replikins.com

24 Rising H9N2 Influenza Replikin Count Has Doubled That of H5N1 (January 15, 2009)

The H9N2 strain of influenza commonly infects poultry and occasionally humans. Replikins, Ltd., using its FluForecast® software, has studied the Replikin Count® annually in each of H9N2 and its sister strain H5N1. H9N2 Count increases occurred in 1996, one year in advance of the H5N1 Hong Kong outbreak, and again in 1999-2000 and 2004-05, 2 years before the subsequent H5N1 Replikin Count increases and outbreaks (see Figure). Cyclic increases and decreases appear to be synchronous for H9N2 and H5N1, with H9N2 increases occurring in advance of, and being greater than those for H5N1. These two strains appear to have a precursor and/or competitor, evolutionary biochemical relationship. H9N2 may be an alternate candidate to H5N1 for the next influenza pandemic.

The Replikin Count® is the number of specific replikin peptides per 100 amino acids in the peak gene of each strain. All sequences published on PubMed worldwide, each year from 1992 to 2008, were studied. Increases in the Replikin Count represent rapid virus replication, and occur in advance of outbreaks (see refs).

The first cycle which has been detected in each virus genome is from 1999 to 2003, and the second from 2004 to 2008. In the second cycle, the maximal Replikin Counts (mean +/-SD) for H9N2 were greater than those in its first cycle, and double those seen to date in all H5N1 and other influenza strains (see refs.). This phenomenon of upregulation of the Replikin Peak Gene in successive replikin cycles in advance of increasing annual human morbidity has also been found by the Drs. Bogoch in West Nile Virus as it entered and expanded into the United States (see refs).

Virus replikins thus provide, to our knowledge, the first quantitative measures of virus structural change ever shown to correlate with and to precede virus outbreaks. Cycles of rapid replication of the virus with increasing replikin counts appear to be a means of virus expansion into new host populations and geographic areas, and of increasing infectivity and lethality.

The data suggests that additional increases in both Replikin Counts and consequent H9N2-H5N1 infections are anticipated in a coming third cycle. Suggesting that a third cycle has begun, after a 5 year absence, H5N1 reappeared in Hong Kong chickens in early December 2008. and an H9N2 infection in a child in Hong Kong was reported on 12/30/2008.

With this new ability to obtain advance virus structural information on coming outbreaks, the rapid (7 day) production of specific effective synthetic replikin vaccines is now possible, as Replikins, Ltd. has reported for a synthetic Taura Syndrome virus oral vaccine 91% protective in shrimp (see refs.).
References and Notes:
Detailed replikins data are published in www.uspto.gov; summaries in 'Replikins Press' <Replikins.com>,.
Replikins, Ltd. now is publishing two monthly e-mail reports by subscription:
1) "FluForecast®" - monthly replikins reports on influenza strains ($1,200. per year); and
2) "ReplikinsForecast®" monthly replikins reports on non-influenza viral, bacterial, trypanosomal, and other emerging infectious diseases ($1,200. per year).
To order, e-mail jmckenney@replikins.com

23 Cancer Mortality Increases With Cancer Cell Replikin Count (December 4, 2008)

Drs. Samuel and Elenore Bogoch of Oncolab, Inc. have found that the concentration of replikins, a new class of peptides in genomic proteins*, are quantitatively related to the mortality rate in human cancer of different cell types. No cancer cell genomic structure has previously been reported to be quantitatively related to mortality rate.

Boston, MA (PRWEB) December 4, 2008 -- Drs. Samuel and Elenore Bogoch of Oncolab, Inc. have found that the concentration of replikins, a new class of peptides in genomic proteins*, are quantitatively related to the mortality rate in human cancer of different cell types. No cancer cell genomic structure has previously been reported to be quantitatively related to mortality rate.

The attached figure shows the relationship between the Replikin Count™ in the Replikin Peak Gene* and the percent mortality in human cancer: the higher the Replikin Count, the higher the percent mortality after 5 years. Glioblastoma multiforme and non-small-cell lung cancer, the two cancer cell types with the greatest 5-year mortality rates in 2002 (98% and 91% respectively), are also the cell types which have the highest Replikin Counts (325 and 250 respectively).

The count in Glioblastoma Multiforme is 18 times higher than the counts in prostate and thyroid cancer which have the lowest Replikin Counts (20 and 15 respectively) as well as the lowest 5-year mortality rates (each approximately 2%). The quantitative relationship of Replikin count to mortality is also seen in the figure for other common cancers, which shows some deviations from an 'ideal' curve. For example, gastric cancer has a higher mortality rate than expected from its Replikin Count (ie shifted to the right), possibly because of the known difficulty of early detection of gastric cancer. Breast and urinary bladder cancer have lower mortality rates than expected from their Replikin Counts (ie shifted to the left), possibly because of the improvement in their early detection and prompt treatment.

To obtain these results, all cancer protein sequences published on PubMed were analyzed by histological cancer cell type by ReplikinForecast™ software. The Replikin Peak Gene (RPGene)* was identified in each cell type. The replikins in each RPGene were counted (Replikin Count = number of replikins per 100 amino acids). The Replikin count of each RPGene then was compared in the different histological cancer cell types as shown in the attached Figure.

Replikin count has already been shown by Replikins, Ltd. to be related to rapid replication, disease outbreaks, and host mortality in viruses such as influenza and HIV, bacteria, malaria, and other infectious diseases*. The relationship between Replikin count and mortality in cancer parallels that found in H5N1 virus in humans and in Taura Syndrome Virus in shrimp.

The authors speculate that in low mortality cancers, it is possible that the immune system may be adequate to the number of invading units; but that the increased mortality rate in viruses and in cancer may reflect the overwhelming of host immune defenses by markedly increased numbers of viruses or of cancer cells produced in each case by increasing replikin concentration in the up-regulated Replikin Peak Gene. An increase in number of cancer cells per unit time produced by rapid replication has been demonstrated in the laboratory in the case of glioblastoma multiforme brain cancer cells in tissue culture*. The quantitative relationship of Replikin Count to mortality rate has been demonstrated in the laboratory in four strains of lethal Taura Syndrome Virus in shrimp*.

These findings have diagnostic, therapeutic, and preventive applications. On the diagnostic side, 1) Oncolab, Inc.'s AMAS®Test, FDA permitted to market and Medicare approved, measures an anti-replikin antibody called the antimalignin antibody useful in the early detection of cancer. 2) Oncolab is now developing a test to determine the lethality of cancer specimens with the use of ReplikinsForecast™ to analyze the replikins in cancer cell protein sequences. Encouraged by the proof of principle demonstration that synthetic replikin vaccines can be effective (91% of shrimp who received an oral synthetic replikin vaccine survived lethal Taura Syndrome virus challenge), synthetic replikin cancer vaccines are currently in development.

*References:

For published detailed antimalignin antibody data by Oncolab,Inc. and the replikins data of Replikins Ltd. studies, see www.uspto.gov. For summaries see replikins.com under "Replikins Press" and Oncolabinc.com. Contacts: Oncolab, Inc. 617-536-9711; Replikins, Ltd. 617-536-0220.

22 A new way to predict outbreaks: replikin peptide concentration in H5N1 influenza virus genome as a marker for lethal outbreaks (November 12, 2008)

WHO and CDC have stated that the predictive accuracy of their annual formulations for human influenza vaccines is "suboptimal" - often correct less than 50% of the time, especially for seniors. Perhaps in part because we are not yet accurate in our predictions of upcoming influenza strains, approximately 36,000 people die each year of flu in the United States alone.

As in the case of hurricanes, early warning of the location and intensity of virus outbreaks would allow us more rapidly and effectively to defend ourselves with strain-specific vaccines. This is now possible.

To provide this vital knowledge, Drs. Samuel and Elenore Bogoch of the Foundation for Research on the Nervous System and Replikins Ltd. of Boston ("Replikins") are presenting new technology at the 7th International Bird Flu Summit in Las Vegas November 13-14, 2008 that can accurately predict which viral strains are poised to attack human populations, and reveal the location from which this viral strain is going to strike. This service is being offered to WHO and CDC.

The key to this predictive technology is a new class of structural virus peptides that have been shown to be involved in the chemistry of rapid replication. The Doctors Bogoch called them "Replikins", and they are strictly defined by the concentration of lysine and histidine residues and the spacing between them. To demonstrate the correlation between the concentration of replikins and the lethality of influenza virus outbreaks, Replikins Ltd. has developed software called FluForecast®, which counts the number of replikins in the sequences of each strain of flu virus across the years - and thanks to the data in public databases like PubMed, we now can track as far as 90 years back.

What Replikins found is that there's a strong correlation between the concentration of replikins and the lethality of an influenza virus outbreak. This allows us to determine in advance, using newly designed software, which viruses have the highest replikin concentrations - and are thus poised to become the most lethal outbreak.

Replikin peptides are not distributed equally throughout the virus genome, but are concentrated in a specific area of the genome designated the Replikin Peak Gene (RPGene). If you graph the replikin counts of the over 14,000 strain-specific RPGenes with lethal outbreaks of particular influenza strains since 1918, you get this:

Note the sky blue lines indicating the low-replikin count for the non-lethal Influenza B. The sky blue lines - and we see them pretty much constantly, as a background flu activity -- these are the "good" ones, for people aren't dying. But where the replikin count grows, things get bad -- such as the H2N2 pandemic in 1957 (that's a dark blue line for that year). Or the H3N2 pandemic of 1968, which is a green line repeating over several years. When the replikin counts for certain viral strains are elevated, we see pandemics - in which one to 50 million people die. Note that the replikins, like the pandemics, are strain-specific.

Which brings us to 2005-6. You can see from the red lines a peaking in the replikin count for human H5N1. From this observation Replikins were able to predict an impending increase in human H5N1 mortality rate. Looking more closely at H5N1 replikin counts in various host species, Replikins observed the following:

In each host group - goose, duck, chicken and human - levels stayed low through 2004. But then Replikins saw a sudden spike in replikins particularly in chicken and human populations in 2005-06, which corresponded with increased epidemics in Asian countries. Which countries? Here again, Replikins looked at H5N1 replikin counts per country:

Low levels of replikin counts - below 4 - were observed in each country until 2005-06, when it spiked most dramatically in Indonesia. Replikins thus predicted that Indonesia would be the first country to experience an H5N1 outbreak with higher human mortality, and this was proven to be correct in 2006-07.

So Replikins have demonstrated that tracking replikin counts not only works historically, but it can predict impending human mortality. Sequence the virus and you can tell whether it's relatively benign or likely to cause a pandemic - the first time this has been possible.

Replikins is offering its FluForecast® service to WHO and CDC as a powerful new tool for tracking the appearance and lethality of new flu strains. By performing prompt replikin analysis of all human influenza sequences as they emerge, we can have advance warning of the intensity and location of future human influenza outbreaks. This will increase the accuracy of annual formulations for influenza vaccines, and will thereby hopefully reduce annual human influenza mortality rates. It is hoped that tracking replikins will save lives.

Beyond prediction, this new replikin-based technology also can be applied to combat influenza - and to develop new vaccines that are more accurate and effective than current technology provides. Replikins have successfully demonstrated this capability when used against a virus in shrimp, which are susceptible to several devastating viral diseases. The replikin-based vaccine developed by Replikins to combat Taura Syndrome virus had a stunning result on the test population, protecting 91% of the shrimp against this deadly virus. Replikin vaccines work orally - and can be synthesized far more quickly than conventional viral vaccines. The vaccine used to save the shrimp was manufactured in seven days. You can imagine what this type of rapid lead time would allow for making on-demand strain-specific influenza vaccines, which with traditional methods must be prepared nine months up to a year in advance.

Replikins is working to expand the capabilities of this vaccine technology and look forward to making significant inroads to control H5N1 and other influenza populations.

Replikins are the viral tool of the future - making accurate predictions in humans and animals now, through the FluForecast® service, and hopefully becoming a front-line weapon to stop viral pandemics in the future.

21 H5N1 Virus Replikin Gene Counts Indicate a New More Virulent Influenza Cycle Has Begun (June, 27 2008)

Replikins Ltd. has found that H5N1 virus replikin peak gene counts in 2007 in Hong Kong, Russia, Indonesia, Vietnam and Israel indicate that a new replikin cycle has begun. The mean replikin count exceeded the maximum of the previous cycle identified by the company. Although several conditions are required to produce a pandemic, the increase in replikin count, a feature of each of the last three pandemics, is now in the range of the increase seen in the 1918 H1N1 pandemic.

Boston, MA (PRWEB) June 27, 2008 -- Replikins Ltd. has found that H5N1 virus replikin peak gene counts in 2007 in Hong Kong, Russia, Indonesia, Vietnam and Israel indicate that a new replikin cycle has begun. The mean replikin count exceeded the maximum of the previous cycle identified by the company. Although several conditions are required to produce a pandemic, the increase in replikin count, a feature of each of the last three pandemics, is now in the range of the increase seen in the 1918 H1N1 pandemic.

FluForecast® software was used to examine all influenza sequences published on PubMed. The area of the genome which contained the highest count of replikins (Replikin Peak Gene, RPG area) was isolated. A major control was obtained in the finding that the replikin count of the RPG area of influenza B virus, which is not lethal, never exceeded a value of 4 in a 67-year period. The first increase in H5N1 virus replikin count in 1996 was found to have preceded the Hong Kong flu outbreak in 1997 (see attached figure). The next increases in H5N1 virus replikin count in 2001, 2002, and 2003 preceded further H5N1 outbreaks and increases in human H5N1 mortality rates. In all countries together, a lower H5N1 virus replikin count occurred from 2004 through 2006, followed by a reduced number of total human cases and deaths confirmed by the World Health Organization. Replikins, Ltd then reported that the cycle of rapid replication for H5N1 which began in 1996 appeared to be over in 2006 ---"until the next rapid replication cycle of this or another influenza virus strain begins".

In 2007, with the replikin count rising to its maximum value to date, a new and perhaps more lethal H5N1 cycle appears to have begun (see figure). In mid-June 2008, the appearance of H5N1 in chickens in markets in Hong Kong prompted extensive culling.

20. Highest replikin concentrations and cyclical behavior related to human mortality are found in malaria trypanosomes (May 19, 2008)

Boston. May 19, 2008. Replikins Ltd. has found that very high concentrations of its replikin genetic sequences are found in the trypanosomes that are the infectious agents in malaria. The levels found by the company are in fact the highest replikin concentrations observed to date in any infectious disease agent. The company has also found that these concentrations cycle over several years.

Replikins appear to be possible agents or promoters of infectivity, host morbidity and mortality. Timely repeated analyses of cyclic changes in an organism's replikin structure may be useful to bring current the targets for the chemical synthesis of ReplikinBestFit™vaccines. These strain-specific vaccines, manufactured in 7 days, were recently shown to protect 91% of shrimp against the lethal Taura Syndrome Virus.

To obtain the current malaria results, publicly-available protein sequence data on Pl. Falciparum, the most common strain in malaria, were gathered from the Pubmed online listing, and examined against World Health Organization data on human malaria deaths for each year between 1986 and 2007. The quantitative replikin concentration (Replikin Count™= number of replikins per 100 amino acids) examined by automated FluForecast® software found those areas of the trypanosome genome which have the highest replikin concentrations (Replikin Peak Genes™).

Two instances of cyclical behavior were revealed in the trypanosome: the first cycle occurred from 1986 to 1995, and the second from 1996 to 2005. The peak of the first cycle, in 1987, with a Replikin Count™ of 38.2 +/-23.5, was followed by a higher peak in the next cycle, in 1999, of 62.9+/-63, exceeding 100 by overlap; both peaks were related to higher human mortality. Counts declined after the 1999 high to a low in 2005 of 7.4+/-6.5; and a decreased mortality rate followed between 2000 and 2005. A third malaria replikin cycle appears to have begun in 2007 with the Replikin Count™ increasing from 7.4+/-6.5 to 17.2+/-19; based on this information, the company is predicting further increases in count and malaria mortality.

Cyclic increases in replikin concentration in the genome can be a mechanism of expansion of an infectious organism into a territory. In other examples, the replikin concentration of West Nile Virus was earlier found to increase annually through two distinct cycles as the virus expanded in the U.S.: the first from 2000 to 2003, and the second from 2004 to 2007 (p less than 0.001). Increases in the annual number of CDC reported human cases followed each of the virus replikin concentration increases. Similar correlations also have been shown for replikin concentrations and human mortality in an influenza H5N1 cycle between 1997 and 2007.

Over the last 10 years, malaria has accounted for more than 10,000,000 deaths worldwide - by comparison, over the same period the H5N1 (Bird Flu) virus has been responsible for less than 300 human deaths. Consistent with the high replikin counts found in this study, trypanosomes have one of the highest replication rates in nature. This property may account in part for the resistance of malaria to previous attempts at vaccination. The discovery of the relation of the replikins to rapid replication offers a new approach, and the means, to inhibit rapid replication and limit mortality in malaria.

19. Cycles of West Nile Virus replikin increases precede increases in the number of human cases (May 1, 2008)

Boston, May 1, 2008. Replikins, Ltd. has found that the replikin concentration of West Nile Virus increased annually through two distinct cycles as the virus expanded in the U.S.: the first from 2000 to 2003, and the second from 2004 to 2007 (p less than 0.001). Increases in the annual number of human cases followed each of the virus replikin increases.

Replikins are peptides found to be specified in virus genomes which increase in concentration signalling rapid replication before virus outbreaks. This is the first report that cyclic increases in virus replikin concentration, each apparently building on the last, can be a mechanism of virus expansion into a territory.

In the present study, virus ReplikinsCount™ by FluForecast™ software was correlated with CDC epidemiological data on the number of human cases per year, permitting discrete cycles to be distinguished within, and correlated between, virus chemistry and host morbidity. The mosquito-born West Nile virus, which incubates between seasons, has been found to increase its concentration of replikins before the next annual step in the cycle of expansion.

The demonstration of replikin cycles represents further 'proof of principle' on the relationship of replikins to virus epidemics and a new means of discerning the course of an epidemic. Previously, increases in the ReplikinsCount™ of the Replikins Peak Gene were found to precede and to predict outbreaks and lethality of two other viruses, influenza H5N1 and Taura Syndrome Virus, in two hosts, human and shrimp respectively. The conservation of specific replikin structures over many years, the detection of new replikins, and the ability to chemically synthesize replikin vaccines in 7 days, demonstrated for H5N1 and Taura Syndrome viruses, have now also been demonstrated for West Nile Virus.

18. H1N1 Influenza Virus with Highest Replikin Count™ Since the 1918 Pandemic Identified in the U.S. and Austria (April 7, 2008)

Replikins, Ltd. has found that the Replikin Count™ of the H1N1 strain of influenza virus has recently increased to 7.6 (plus/minus 1.4), its highest level since the 1918 H1N1 pandemic (p value less than 0.001). A rising Replikin Count of a particular influenza strain, indicating rapid replication of the virus, is an early warning which has been followed consistently by an outbreak of the specific strain. The current increase appears to be specific to H1N1; there was a concurrent 80% decline in the Replikin CountTM of H3N2, for instance.

Boston, MA (PRWeb) April 7, 2008 -- Replikins, Ltd. has found that the Replikin Count™ of the H1N1 strain of influenza virus has recently increased to 7.6 (plus/minus 1.4), its highest level since the 1918 H1N1 pandemic (p value less than 0.001). A rising Replikin Count of a particular influenza strain, indicating rapid replication of the virus, is an early warning which has been followed consistently by an outbreak of the specific strain. The current increase appears to be specific to H1N1; there was a concurrent 80% decline in the Replikin Count of H3N2, for instance.

The current H1N1 appears to be rapidly replicating simultaneously in the U.S. and Austria. It may succeed H5N1 as the leading candidate for the next expected overdue pandemic. However, the same virus replikin structures detected by FluForecast® software in all three previous pandemics, namely 1918 H1N1, 1957 H2N2, and 1968 H3N2, as well as in H5N1, have not yet been detected in the currently evolving H1N1.

There is evidence that many factors, including virus structure, host receptivity, and the environment, together with infectivity and rapid replication, need to converge for a pandemic to occur. For H5N1, the high human mortality rate, which peaked at over 80% in 2006-07 in Indonesia, as well as current low infectivity, both appear to limit H5N1's ability to produce a pandemic. Furthermore, the H5N1 rapid replication cycle which began in 1996 now appears to be over. The H5N1 virus produced less than 300 World Health Organization confirmed deaths over the past 10 years.

On the other hand, H1N1, with an estimated human mortality rate of only 2.5 to 10%, but with much higher infectivity, produced an estimated 50 million deaths in the 1918 pandemic. A number of countermeasures exist today which did not exist in 1918, however. Among these is Replikins' ability to manufacture synthetic vaccines based on current sequences, with a seven day production turnaround.

17. Replikins Oral Vaccine Synthesized in 7 days protects 91% of Shrimp Against Lethal Virus (March 11, 2008)

Replikins, Ltd. has announced development of a chemically synthesized vaccine specific to a Taura Syndrome virus structure based on its patented Replikins™ technology. When the vaccine was administered orally to shrimp, 91% survived a challenge by the lethal Taura virus. The effectiveness of this vaccine, and its rapid production cycle (7 days), represent an important proof of concept for developing vaccines against a range of rapidly replicating high lethality virus outbreaks.

Boston, MA (PRWEB) March 11, 2008 -- Replikins, Ltd. has announced development of a chemically synthesized vaccine specific to a Taura Syndrome virus structure based on its patented Replikins™ technology. When the vaccine was administered orally to shrimp, 91% survived a challenge by the lethal Taura virus. The specificity of the protective effect was established in control groups by chemically blocking the active regions in the vaccine, and as a result the protective effect was lost in these control groups. The effectiveness of this vaccine, and its rapid production cycle (7 days), represent an important proof of concept for developing vaccines against a range of rapidly replicating high lethality virus outbreaks.

For counteracting emerging infectious disease, early detection and rapid response are critical. Replikin contributions to date are both in early detection and rapid response: 1) Advance warning previously was not possible until it was found in H5N1 influenza that an increase in the virus replikin concentration signalled one year in advance that the outbreak was coming, and indicated the country in which this would occur (FluForecast™, Indonesia). 2) The production of vaccines by other methods has required 3 to 12 months, by which time the epidemic may have come and gone, or the vaccine effectiveness reduced or lost because the target changed due to mutation. In contrast, the replikins vaccine found effective here was manufactured synthetically in 7 days.

Viruses lethal to shrimp have been responsible for large losses to aquaculture worldwide. Replikins is forming a division to focus on these viruses. The company is also pursuing development of synthetic vaccine products based on replikin epitopes, Syntopes™, for the control of fish hemorrhagic viruses and other lethal aquatic microorganisms.

16. FluForecast® Replikin Count™ Predicts That The H5N1 Cycle Which Began In 1996 is Now Over (February 11, 2008)

Replikins Ltd. announced that the quantitative analysis of Replikin Count™ in the virus gene structure predicts that the current H5N1 cycle is over. Sporadic outbreaks may continue, but the rapid epidemic spread and high mortality characteristics are expected to subside - until the next rapid replication cycle of this or another influenza virus strain begins.

Boston, MA (PRWEB) February 11, 2008 -- Replikins Ltd. announced that the quantitative analysis of Replikin Count™ in the virus gene structure predicts that the current H5N1 cycle is over. Sporadic outbreaks may continue, but the rapid epidemic spread and high mortality characteristics are expected to subside - until the next rapid replication cycle of this or another influenza virus strain begins. 140,000 virus protein sequences were analyzed by FluForecast® software in this study. A key gene, the Replikin Peak Gene, was found to contain the highest concentration of replikins in the virus genome. In H5N1 reservoirs in chickens, the Replikin count has now decreased markedly, successively each year from 2004 to 2007. The Replikin count in human H5N1 also has decreased in the past year. All stated increases and decreases were statistically significant with a p value of less than 0.001.

The current H5N1 cycle of bird flu began in 1996 with a pre-symptomatic increase in the Replikin count, followed in 1997 by the Hong Kong outbreak, then by a decline in Replikin count in 1998-1999 with culling, followed by increases in the count in 2001 and 2004 providing advance warning of the further outbreaks which occurred in Asia. An increase in the Replikin count in human H5N1 in 2006 specifically predicted the increase in H5N1 lethality in humans, and that the first country to show this increase would be Indonesia. These predictions were proven correct in 2006-2007.

The last two influenza pandemics of 1957 (H2N2) and 1968 (H3N2), and the SARS outbreak of 2003, were also each preceded by an increase in the Replikin count, and in each case, a strain-specific decrease in the count several years later signalled that the cycle was over. Sporadic outbreaks of H3N2 for example have occurred thereafter, but the rapid epidemic spread and high mortality characteristics have not reappeared.

It has not been possible previously to predict in advance from changes in the structure of the virus the coming of epidemics or their cessation. This is now possible because of the discovery of the replikins, specific small peptide constituents of virus proteins whose concentration has been shown to be related quantitatively to rapid replication and epidemics.

15. Lethal Human H5N1 Influenza Virus Replikin Gene Still Upregulated (December 11, 2007)

Replikins, Ltd. today announced its latest findings regarding the virus replikin count in human H5N1 influenza virus. The company's software-driven analysis has found that the prevalence of these sequences has remained high in Indonesia; in addition, higher counts now have been found in China. These statistics reflect an "upregulation" of this gen e which has been linked to the lethality of influenza viruses. When factored in with previous findings, this suggests that the H5N1 outbreak in Indonesia is not over and that the next country to show an increase in human cases and mortality rate will be China.

Boston, MA (PRWEB) December 11, 2007 -- Replikins, Ltd. today announced its latest findings regarding the virus replikin count in human H5N1 influenza virus. The company's software-driven analysis has found that the prevalence of these sequences has remained high in Indonesia; in addition, higher counts now have been found in China. These statistics reflect an "upregulation" of this gene which has been linked to the lethality of influenza viruses. When factored in with previous findings, this suggests that the H5N1 outbreak in Indonesia is not over and that the next country to show an increase in human cases and mortality rate will be China.

This is the second of a series of reports on the use of a new methodology to isolate 'in silico' and to track and control specific replikin gene activity in several disease states.

A software method, called FluForecast®, has been designed to measure Replikins™, a class of proteins containing high concentrations of amino acids lysine and histidine, that have been determined to be related to rapid replication and virulence. Rather than being evenly distributed in the virus genome, replikins have been found to be concentrated in specific genomic areas. The area of each genome with the highest concentration of continuous replikin peptides has been isolated in silico and named a Replikin Peak Gene (RPG). Using proprietary computer algorithms constructed to identify, count, and track historically this class of proteins, replikins have now been analyzed in 130,488 protein and genome sequences. These include all the accession numbers for common strains of influenza and other lethal virus isolations published between 1917 and 2007 in the PubMed repository. The method is being applied to the diagnostic and therapeutic control of virus and bacterial diseases.

When the replikin count of the SARS virus dropped in 2003, it signalled correctly that the SARS outbreak shortly would be over. Similarly for each of the influenza pandemics and epidemics of the last century, for which the replikin count had been elevated before and during those outbreaks, decrease in the strain-specific replikin count which was causing the outbreak gave advance notice that the outbreak was over. For H5N1 influenza, each of the onsets and cessations of the outbreaks from 1997 to the present were correctly predicted by the replikin count. In 2006 a drop in the number of human H5N1 cases gave rise to optimism that the H5N1 human outbreak might be over; the replikin counts rose at that point, however, and the outbreak has continued. In addition, comparison of replikin counts for virus specimens in several countries showed that the highest counts were in Indonesia. In 2006 Replikins also announced its prediction that the percent mortality in humans due to this virus, rather than declining, would in fact increase, and that the first country in which this would occur would be Indonesia. In 2007, both of these predictions made in 2006 were shown to be correct.

The current persistence of the upregulation of the H5N1 replikin peak gene in Indonesia, and its additional increase in China, support continuing efforts to organize public health measures and to prepare appropriate anti-viral drugs and vaccines.

Detailed data from these studies are published in issued and pending patents. FluForecast® is a product and service of Replikins Ltd. and Replikins,LLC., 38 The Fenway, Boston MA 02215. See also http://www.replikins.com.

14. AMAS Test Measures Lethal Replikin Gene Activity in Lung and Other Cancers (December 6, 2007)

A gene related to rapid replication and lethality has been found to be present in, and to contain some identical protein sequences in, tobacco mosaic virus and non-small cell lung cancer. The early detection diagnostic test for cancer, the AMAS® test, appears to measure this gene's activity.

Boston (PRWEB) December 6, 2007 -- A gene related to rapid replication and lethality has been found to be present in, and to contain some identical protein sequences in, tobacco mosaic virus and non-small cell lung cancer. The early detection diagnostic test for cancer, the AMAS® test, appears to measure this gene's activity.

This is the first of a series of reports on the use of a new methodology to isolate 'in silico' and track specific gene activity in normal and several disease states.

This newly identified gene has been named the Replikin Peak Gene (RPG). "Replikins"™ are a class of proteins containing high concentrations of amino acids lysine and histidine that have been previously determined to be related to rapid replication and virulence. Using proprietary computer algorithms constructed to identify, count and track historically this class of proteins, replikins have now been analyzed in 130,488 protein and genome sequences. These include all the accession numbers for common strains of influenza and other lethal virus isolations published between 1917 and 2007 in the PubMed repository. Replikins have been found to be concentrated in specific genomic areas. The area of each genome with the highest concentration of continuous replikin peptides has been isolated in silico and named a Replikin Peak Gene (RPG).

Specific RPGs have been identified and quantified in infectious organisms including viruses, bacteria and trypanosomes (malaria). 'Upregulation' of the Replikin Peak Gene is evidenced by an increase in the replikin count in the RPG, that is, in the number of replikins per 100 amino acids. For example, in the case of influenza B, which has not to date been lethal, a low replikin count (less than 4) always occurred in influenza B RPGs between 1940 and 2006; and in quiescent periods of influenza A. In contrast, the replikin counts in lethal influenza A virus RPGs increased to over 20, from as much as one to three years before and during outbreaks. Strain-specific increases in replikin count have appeared in relation to the major influenza pandemics and epidemics, after years of constant low stable counts. Furthermore, a high replikin count of the RPG of an organism has been shown to be associated consistently with a higher percent lethality in the host. The increase in count was frequently detected one year or more before the outbreak was clinically apparent. The ability to identify, count and track replikins in the genomic structure of an emerging organism has been shown to be accurately predictive in advance warning of H5N1 outbreaks, and may have value in the management of influenza epidemics.

The highest replikin count of the RPG found in any organism studied to date is in lethal non-small cell lung cancer. The highest AMAS test results found to date also are in lung cancer. Tobacco mosaic virus has some sequences in its RPG that are identical to those in the RPG in non-small cell carcinoma of the lung. Two structural studies have suggested mobility and inter-organism transfer of replikins associated with lethality.

Replikins have been chemically synthesized and were found experimentally to be immunostimulants, producing strong antibody responses in animals. Synthetic cancer replikins administered to animals produce antibodies that can be measured by the AMAS cancer test. The AMAS test's results are evidently related to the rate of replication in the cancer. In short, the AMAS test measures the activity of the replikins that are unique to cancers, whose concentration is related to lethality.

High replikin counts are present in a wide range of lethal diseases. The structural and functional relationship found between the replikin peak genes of the tobacco mosaic virus and non-small cell lung cancer is one illustration of the relationship between replikin count, rapid replication and virulence. Possible implications of these findings of the same replikin structures and functions in tobacco mosaic virus and lung cancer are under further study.

Detailed data on these studies are the subject of issued and pending published patents and are being presented today at a seminar in New York by Samuel Bogoch, M.D., Ph.D.

13. Replikins, LLC Finds West Nile Virus Replikin Count Has Reached Its Highest Recorded Value (August 3, 2007)

Replikins LLC's analysis of the West Nile peptides has provided advanced warning of the increase of West Nile Virus occurrence now beginning to be reported. Advanced warning of the cyclic build-up of West Nile Virus (WNV) is important as preventive measures against the virus's mosquito carrier could be timely activated.

Boston, MA (PRWEB) August 3, 2007 -- Replikins LLC. has discovered a new group of virus structural peptides within virus proteins, called replikins, which provide virus-specific advance quantitative warnings of rapid replication and the risk of epidemics. Replikins LLC has developed software called ReplikinsForecastTM, which quantitatively measures the concentration of these specific peptides in virus proteins (Replikin Count™). Increased Replikin Counts give advanced warning by frequently preceding a virus outbreak by one or two years, and return to lower levels in advance of quiescent periods. Analysis just completed by Replikins LLC of the most currently available West Nile virus protein sequences world wide listed on PubMed indicates that the Replikin Count™ has increased over the past seven years to reach in 2006 its highest level recorded, indicating the potential for even more severe West Nile Virus outbreaks with higher mortality rates to come.

The CDC has commented on the inability to date to predict eruption of outbreaks or their magnitude: "We know there are going to be focal areas that are going to be outbreak areas, but we can't guess where or what magnitude they're going to be" (reference 1). "Yet despite nationwide efforts to fight and track West Nile virus, it can't be predicted whether the mosquito-borne disease is poised to increase, decline or erupt in occasional outbreaks now that it has settled in across the nation" (reference 2).

Replikins, LLC is regularly making accurate predictions for influenza viruses (reference 3) and according to the present findings, may also be able to do so for West Nile Virus. The methodology previously used successfully by Replikins LLC with influenza viruses, has now been applied to West Nile Virus. The Replikin Count of WNV (number of replikins per 100 amino acids) has been found to have increased from 2.8 in 2000, to 3.8 in 2004, to 4.5 in 2005, to 6.0 in 2006 (statistically significant, p values < 0.001). If the relationships to outbreaks previously demonstrated for influenza virus replikins apply as well to West Nile Virus replikins, this data indicates that the immediate prospect is for more severe West Nile Virus outbreaks with higher mortality rates.

ReplikinForecast™ is a proprietary exclusive service offered by Replikins LLC. and Ltd. for the advanced warning of, and to track, emerging viruses and other infectious organisms. In Replikins's Early Warning/Rapid Responset™ Service, virus protein sequences of threatening viruses, as soon as available, are analyzed within hours(reference 4).

NOTES

1 The Arizona Republic, July 19, 2007

2 Sacramento Bee, July 31, 2007

3 High Replikin Counts in H5N1 virus are associated with high mortality in humans infected with H5N1. In the laboratory, high Replikin Counts in Taura shrimp viruses are also quantitatively related to high mortality rates in shrimp (p < 0.001). The virus Replikin Peak Gene (RPG), that section of the virus genome which contains the highest concentration of replikins (p < 0.001), also has been isolated in silico. Analysis of RPG permits a more accurate forecast, and comparison of the virulence of the current and past versions of the organism. (see Replikins' website for more information).

Earlier work by Replikins LLC on influenza has shown that the concentration of replikins in the virus correlates quantitatively with each of the pandemics and major outbreaks of influenza virus since 1918, and has predicted prospectively each of the outbreaks of H5N1 bird flu virus since 2000. When H5N1 was thought by some investigators to be quiescent, FluForecast®, using the Replikin Peak Gene, predicted in 2006: 1) that a higher human mortality outbreak was imminent, and further: 2) that the primary country in which this outbreak would occur would be Indonesia. In 2007, both these predictions were found to be correct. To our knowledge, no other methods are available which could accurately have made these predictions.

4 Replikins LLC also has strain-specific synthetic vaccines in development, which based upon the replikins analysis have been tailored, produced and delivered for testing in days.

12. Indonesia Reports Experiencing Human H5N1 Mortality Increase, as Predicted Last Year by Replikins' FluForecast® Quantitative Virus Analysis (June 8, 2007)

Recent interviews with Indonesian health officials indicate that two key predictions made in 2006 by Replikins' proprietary epidemic forecasting software were correct - that a strain of H5N1 Bird Flu with increased virulence would emerge in 2007, and that it would emerge in Indonesia. The company plans to parlay this success into further contracts with governments and corporate vaccine groups.

Boston, MA (PRWEB) June 8, 2007 -- The results published in 2006 by Replikins, Ltd. showed that 2005-2006 FluForecast® virus data indicated clearly that 1) the mortality rate of human H5N1 was increasing markedly, and that 2) the first country in which this would be clinically realized would be Indonesia.

Two days ago, Bayu Krisnamurthi, the head of Indonesia's avian flu control commission, reported the clinical realization of both of these two predictions (Canadian Press, June 6, 2007). In his comments to reporters, Dr. Krisnamurthi stated that recent changes in the H5N1 virus seem to be increasing its rate and ease of transmission from birds to humans.

The World Health Organization (WHO), which has not yet used the FluForecast® Service, has reported that as yet they had no evidence of these changes. FluForecast, an automated software-based system for pinpointing genomic changes in viruses, is the only system which has successfully predicted, well in advance, each outbreak of H5N1 bird flu over the past seven years. Recent discovery of the Replikin Peak Gene and improvements in its Replikins' patented technology have allowed prediction of the geographic location, as well as the gene location and the host animal species of each outbreak. The announcement by Dr. Krisnamurthi represents the first independent government confirmation of the success of these improved capabilities.

This new Replikins, Ltd. service is now being applied to other viruses and other infectious organisms. The company's services are available both to government organizations and pharmaceutical companies.

11. FluForecast Trial in 2006 Predicted High Human H5N1 Mortality in Indonesia (May 9, 2007)

When H5N1 was thought to be quiescent in 2006, in a prospective open trial, FluForecast®, a software program which measures virus gene proteins, predicted high human mortality H5N1 outbreaks to come2. In addition, FluForecast technology predicted that the leading country in which these outbreaks would occur would be Indonesia. Both predictions have now been found to be correct. The basis of these predictions, that unique virus structures relate quantitatively to high host mortality, has now also been demonstrated independently in laboratory experiments.

Boston (PRWEB) May 9, 2007 -- When H5N1 was thought to be quiescent in 2006, in a prospective open trial, FluForecast®, a software program which measures virus gene proteins, predicted high human mortality H5N1 outbreaks to come2. In addition, FluForecast technology predicted that the leading country in which these outbreaks would occur would be Indonesia. Both predictions have now been found to be correct. The basis of these predictions, that unique virus structures relate quantitatively to high host mortality, has now also been demonstrated independently in laboratory experiments.

The FluForecast software program, developed by Replikins Ltd. to give advanced warning of influenza outbreaks, measures quantitatively the concentration of a new class of virus peptides, called Replikins, shown to be related to rapid replication and epidemics. (see footnotes 1,2, and 3). FluForecast has been used to identify, or isolate 'in silico', the area of the virus genome which contains the highest concentration of replikins; this area is now called the Replikin Peak Gene. It has now become possible to measure quantitatively the replikin concentration (Replikin Count, or number of replikins per 100 amino acids) in the Replikin Peak Gene (RPG) of all H5N1 virus isolates whose amino acid sequences are published annually in PubMed. It is now possible to determine whether the RPG gene in a given virus isolate is relatively 'quiescent' or more active, i.e. 'upregulated'.

While the Replikin Count of the whole virus had previously been found by Replikins, Ltd. to correlate with virus epidemics and outbreaks, the RPG gene, with a four-fold concentration of replikins, magnifies the differences. It is also now possible to compare the RPG in different hosts. The H5N1 virus RPG in humans has increased nine-fold from 2004 to 2006, and in 2006 was found to exceed the RPG in other hosts, eg. goose, duck and chicken. Similarly, it was possible to compare the RPG in each country, for each host. In this way it was found that the RPG upregulation in Indonesia for human H5N1 in 2006 was more than double that in Thailand and three to six times that in Japan, Russia, China and Vietnam. Thus the data in 2006 predicted both higher H5N1 human mortality rates, and that this would occur predominately in Indonesia. Both predictions have been realized in 2007 (footnote 4).

In addition to these epidemiological studies, the hypothesis that host mortality rate can be predicted by virus Replikin Count has now been tested and confirmed in the laboratory. For each of four strains of Taura syndrome virus of shrimp, the Replikin Count was determined and compared by FluForecast. Separately, the laboratory determined blind, that is without knowledge of the order of virulence predicted by replikin analysis, the comparative actual mortality rates in shrimp achieved by each of the four virus strains. In the laboratory, these four strains were found to have increasing mortality rates in the following order: Venezuela, Hawaii, Thailand and Belize. Point-to-point linear statistically significant correlation was found between the Replikin Count and the mortality rate of each of the four strains.

Footnotes: 1 Bogoch S and Bogoch ES. Replikins: The Chemistry of Rapid Replication.Begell Press, New York, 2005. 2. website: replikins-dot-com 3. FluForecast® is a service of Replikins, Ltd. 4. World health Organization: Earth Times.org. April 26, 2007; ScientificAmerican.com. May 6, 2007; VOA News.com, May 7,2007; Jakarta Post, May 8, 2007. 5. In the first quarter of 2007, the quantitative FluForecast Replikin Count for the Replikin Peak Gene of human H5N1 virus has not yet decreased, as it has been found to do when other influenza epidemics have run their course.

10. High Host Mortality Rate Quantitatively Related to High Virus Replikin Count (March 6, 2007) 

In a presentation at the World Aquaculture Conference in San Antonio, Texas, Replikins Ltd. reported that the concentration of replikin genome elements in five different viruses - human H5N1 influenza and shrimp 4 strains of Taura virus - is quantitatively related to percent mortality in two different hosts, humans and shrimp respectively.

San Antonio, Texas (PRWeb) March 6, 2007 -- A major challenge in virus epidemiology and prevention is the difficulty of identifying which gene fragments contained in different virus strains are likely to pose a serious health risk, both in animals and humans.

In a presentation at the World Aquaculture Conference, held at the San Antonio Convention Center, Dr. Samuel Bogoch, Chairman of Replikins, reported results of recent studies which show that the higher the Replikin Count™ of the virus, the higher the mortality rates of the host. Replikin counts™ were defined as the number of replikin peptide sequences per 100 amino acids in th genome of the virus under study.

In the animal portion of the presentation, Dr. Bogoch reported early results of an ongoing research collaboration aimed at identifying the lethality of different sub-strains of the shrimp Taura virus. In the human portion, higher Replikin counts™ were associated with higher death rates in current strains of the H5N1 Bird Flu virus.

This is the first instance of virus protein structure shown to be quantitatively related not only to the occurrence of epidemics but now specifically to mortality rate of the host. Streaming video of the presentation is available at Scitalks, the video website for science talks and presentations: http://scitalks.com/index.php?category=search&search=bogoch

Contact:

Samuel Bogoch, M.D., Ph.D.
Chairman
Replikins Ltd.
38 The Fenway
Boston MA 02215
Ph. 646-320-5910
sbogoch@replikins.com

Carol Zepp,
PR 101
Ph. 978-500-5030

9. Gene Segment Identified in Virulent Human H5N1 Viruses - Key Discovery May Enable Development of Vaccines, Therapeutics (January 25, 2007) 

Viruses whose genomes constantly mutate, such as the H5N1 "bird flu", are driving a race to find relatively unchanging segments of their genomes; successful identification of these segments may allow more successful vaccines and therapeutics to be developed.

Boston (PRWeb) Januarary 25, 2007 -- Viruses whose genomes constantly mutate, such as the H5N1 “bird flu”, are driving a race to find relatively unchanging segments of their genomes; successful identification of these segments may allow more successful vaccines and therapeutics to be developed.

Replikins are short fragments of the genomes of infectious organisms, which have been found to be related quantitatively to rapid replication and epidemic outbreaks (1,2). Scientists at Replikins, LLC have just identified a specific site in the human H5N1 virus genome which contains a dramatically higher concentration of replikins than the rest of the virus, and named it the Replikin Peak Gene™ (RPG).

Two of the replikin components of RPG have been found to be conserved over 88 years in the following high-mortality and pandemic virus strains: H1N1, H2N2, H3N2, H5N1, and H7N7. This discovery makes possible very specific targeting with vaccines and other treatments; these Replikin peptides also form the basis for a pan-strain influenza vaccine, for which trials are underway.

New quantitative virus protein sequence search software, FluForecast, available as a service from Replikins Ltd., was central to this work. RPG was isolated by comparing the replikin concentration (Replikin Count™) of RPG to seven other defined areas of the H5N1 genome (Figure). The Replikin Count™ of RPG was found to be associated with the pB1 area of the human H5N1 virus genome, and was increased tenfold from 2003 to 2006, during the current bird flu epidemics, when it was 4 to 10 times greater than that of the other genomic sections of the virus (hemagglutinin, neuraminidase, pA, pB2, ns, matrix, nucleocapsid) (p less than 0.001). In contrast to 'in vivo' or 'in vitro' localization of a gene, this method may be thought of as “in silico” identification or isolation of a gene.

Contact:

Samuel Bogoch, M.D., Ph.D.
Chairman
Replikins Ltd.
38 The Fenway
Boston MA 02215
Ph. 646-320-5910
sbogoch@replikins.com

Carol Zepp,
PR 101
Ph. 978-500-5030

8. Human H5N1 Virus Replikin Count overtakes levels in H5N1
'Bird Flu' (December 27, 2006) 

A common question asked at current scientific conferences is: 'where did bird flu go?' The recent decrease in reported H5N1 human cases and bird outbreaks might indicate that the virus has become dormant. However, quantitative analysis by Replikins, Ltd. of human H5N1 virus sequences in 2006 has found that the Replikin Count™ has significantly increased beyond all annual previous levels reported in chickens and humans.

Boston, MA (PRWeb) December 27, 2006 - A common question asked at current scientific conferences is: 'where did bird flu go?'

The recent decrease in reported H5N1 human cases and bird outbreaks might indicate that the virus has become dormant. However, quantitative analysis by Replikins, Ltd. of human H5N1 virus sequences in 2006 has found that the Replikin Count™ has significantly increased beyond all annual previous levels reported in chickens and humans. The Replikin Count™ determined by virus protein software analysis, provides an index of the capacity for virus rapid replication. The Replikin Count™ is defined as the number of replikin peptide sequences per 100 amino acids of virus protein, that is concentration, and is independent of the number of specimens examined.

Rather than declining, the Replikin Count™ in humans in 2006 has risen 35% over that in 2005, and outstripped the Count in all reported chicken H5N1 virus specimens, both with reference to the mean and the range, of the peptideWith the rise in Replikin Count™ in human H5N1, (3.7(+/-4.1) in 2005 to 5.0(+/-5.9) in 2006, p<0.002), the human Count exceeds that for H5N1 in chickens, which after rising from 2003, has been constant (3.2(+/-2.8) in 2005, and 3.2(+/-3.1) in 2006. The Replikin Count™ in H5N1 is now seen to have risen steadily, by a factor of 3.9 from the 1998 Replikin Count™ of 1.3(+/-0.4) in chickens to the Replikin Count™ in humans in 2006 of 5.0(+/-5.9) (p<0.001). The Replikin Count in the 1918 H1N1 influenza pandemic was 7.0. The mortality rate in human H5N1 cases has also increased 2.3 times, from 26 percent in 1997-98 to approximately 60 percent in 2006.

The increase in Replikin Count™ could have provided early warning of the last three H5N1 bird outbreaks (2001-2006). It was also found to precede or was an early association of the three influenza human pandemics (1918 (H1N1), 1957 (H2N2) and 1968 (H3N2), and the H5N1 outbreak in Hong Kong (1997) (see www.replikins.com for detailed data).

In contrast to H5N1, Replikin Count™ analyses of H3N2 influenza virus (the cause of the pandemic of 1968) has decreased (2.7(+/-0.6) in 2005 to 0.8(+/-1) in 2006, p<0.001). Such decreases have been associated with periods of relative viral quiescence.

“This rise in human H5N1 Replikin Count suggests that the replication rate of this virus in humans continues to increase. Humans may be becoming a preferred host for H5N1” according to Dr. Sam Bogoch, Chairman of Replikins, Ltd.   

“The Replikin Count™ is specific to the virus strain, the host species, and the region, and can be used to indicate the threat level of a particular virus. We know of no other quantitative measures of particular peptide sequences of virus proteins, or of any other chemical constituent, which have this correlative and predictive value” he said. 

In addition to FluForecast®, Replikins, Ltd. has enlisted an international ‘Replikins Group’ of several universities and research institutions to test the effect of its potential synthetic replikins vaccines and other products against these new targets related to rapid replication in H5N1 and other virus disorders.

Contact:

Samuel Bogoch, M.D., Ph.D.
Chairman
Replikins Ltd.
38 The Fenway
Boston MA 02215
Ph. 646-320-5910
sbogoch@replikins.com

Carol Zepp,
PR 101
Ph. 978-500-5030

7. Rising Human H5N1 ‘Bird Flu’ High-Virulence Sequences Found By Replikins, Ltd. (November 6, 2006)

BOSTON, November 6 /PR Newswire/ —  Replikins, Ltd. has completed a comprehensive quantitative analysis of H5N1 ‘bird flu’ peptide sequences found in humans infected with H5N1 in the past nine years.

The data, obtained from public sources, included 1,455 complete sequences from human specimens. The company has found a continuous and statistically significant increase in the concentration of peptide sub-sequences (previously linked to epidemics) in the H5N1 virus over the past nine years, suggesting a heightened potential for an epidemic outbreak in humans. The replikin concentration in H5N1 has been found to rise steadily, by a factor of 2.5 over the period covered, from 1997 to 2006, from a mean count of 1.9 to the current count of 4.8 units per 100 amino acids (Replikin Count™).

Over the period covered by the study, the mortality rate in human H5N1 cases has in fact also increased by a multiple (2.3 times), from 26 percent in 1997 to 60 percent in 2006, a rise comparable to the increase in the concentration of the replikin sub sequences.

While a direct causal relationship has not yet been shown, each previous increase in the concentration of replikin protein sub-sequences in flu viruses has been associated with strain-specific influenza epidemics that have occurred in the great pandemics of the last century: in 1918, 1957 and 1968. The same structure of the replikin peptide  
sub-sequences in influenza now can be traced back from the present to 1917. This conserved structure may be a  key to the design of synthetic vaccines whose composition would not have to be changed every year.

Using proprietary technology, Replikins, Ltd. has discovered and defined a group of virus protein sub-sequences – called replikins – which can be used to predict whether a virus is rapidly replicating and whether it is likely to spread.

Replikins, Ltd. has also developed software (FluForecast®) which can now detect and count these proteins, which may allow scientists to better predict outbreaks of viral epidemics including H5N1.

Such predictions have been made correctly in advance by the company for the last three ‘bird flu’ (H5N1) outbreaks from 2002 to the present. Prior to this discovery, no protein or other biological phenomenon has been found to correlate directly and quantitatively with viral epidemics. As a result, researchers have had no means to predict if, and what strain of a given viral organism will become a public health threat. The current concern over when or if there will be an avian flu epidemic in humans has drawn attention to the need for improved measures to help predict, prevent and prepare for emerging health threats.

Dr. Sam Bogoch, Founder of Replikins, Ltd. explained that the finding in human H5N1 virus is significant because, “Combined with the software that analyzes viral strains, we now — for the first time — have an objective quantitative means of determining the threat level of a virus.” 

“To our knowledge, there is no other product which provides this quantitative predictive information.” In explaining how the Replikins proteins were identified Dr. Bogoch, who also founded the Neurochemistry Laboratory at Harvard Medical School, said, “After discovering the relationship of the structure of the sub-sequence replikin peptides to rapid replication in other infectious organisms, we focused on the influenza virus, because the CDC has epidemiological data available going back nearly 100 years. We discovered that a consistent sub-sequence of peptides increased in concentration in all influenza virus outbreaks.”

6. Advance Warning Of H5N1 Influenza Outbreaks May Be Found In Shrimp Virus Reservoirs (Oct 26, 2006)

Researchers at Replikins, Ltd.[1] have discovered that the shrimp viruses White Spot Syndrome virus (WSSV) and Taura Syndrome virus (TSV) - global lethal pathogens for shrimp - may be reservoirs for the peptide building blocks of H5N1, or bird flu virus.

The H5N1 virus recently has been responsible for huge poultry losses in many countries and for several hundred human cases, with approximately 50% mortality. While migratory waterfowl are known to transport the H5N1 influenza virus globally, no reservoirs for this virus have been identified[2].

Using FluForecast® proprietary technology, Replikins, Ltd. researchers have identified a new group of virus peptides of specific structure, called "replikins." The concentration of replikins in a virus (quantitative Replikin Count) has been shown to be related to rapid replication, and to be increased in epidemics and in the last three influenza pandemics[1]. Quantitative determination of the concentration of virus replikins by FluForecast®, the company's proprietary software, has made it possible to predict in advance the recent H5N1 outbreaks[1].

Replikins, Ltd. researchers found that shrimp viruses also contained replikins, and asked if there might be a relation between shrimp viruses and H5N1 influenza virus in waterfowl.

Using FluForecast®, the following findings were obtained which suggest that shrimp viruses may serve as one reservoir of replikin peptide building blocks for H5N1 and other influenza strains:

1) Shrimp viruses WSSV and TSV were found to contain replikin peptide sequences.

2) These shrimp virus sequences were found to be related in structure to the replikin peptide sequences in H5N1 virus.

3) Shrimp WSSV replikins increased markedly in concentration in the year 2000, just before the increase in H5N1 virus Replikin Counts which preceded the H5N1 outbreaks in chickens and humans of 2001-20061. The increase in shrimp virus Replikin Count was not trivial: In shrimp WSSV, which in dormant states was found to be less than 10 in the year 2000, reached 103.8. This is comparable only to the highest Count so far observed in any organism in nature. (The highest Replikin Count to date of 111 has been observed in the malaria species, pl. falciparum, which replicates 11,000 times in 48 hours passing from liver to blood in the host.)

4) Of the new shrimp replikins which appeared in 2000, the percent which were short peptides was increased compared to dormant years. Short replikins previously have been found to be related to high virulence and high mortality in the host, whether animal or man.

5) These short shrimp virus replikins share structures with short replikins in both H5N1 and other influenza strains going back 88 years to the great pandemic of 1918.

A related example of virus reservoir activity in which the replikin concentration was increased preceding an outbreak was found in the corona viruses as a group. The Replikin Count of the corona virus group increased markedly in 2002 before the outbreak of one of its members, SARS, in 2003[1]. In another study, further confirming the relationship of Replikin Count to rapid replication, studies on replikins in two strains of human HIV-1 virus have shown that the Replikin Count of a rapidly replicating strain is sixfold greater than that of a slowly replicating strain. No instances of rapid replication have been observed in all the organisms examined in which the Replikin Count was not significantly increased compared to the Count in the dormant state.

Advance forecasts of virus outbreaks, now possible with FluForecast®, have not previously been possible. The relation of Replikin Count to rapid replication will be further used to examine virus reservoirs in both poultry and aquatic organisms for coming influenza outbreaks in animals and humans. Such forecasts now may permit time for preventive public health measures to be mobilized and safer strain-specific vaccines to be synthesized, tested, and mass produced.

Replikins, Ltd. is providing FluForecast® services to others. The "Replikins Group" has been formed with a number of university, government, and pharmaceutical institutes to test new synthetic Replikin vaccines developed by Replikins, Ltd. which target rapid replication in emerging viruses and a range of other infectious diseases.

5. Replikins' FluForecast Software Pinpoints Change in Deadly Bird Flu Amino Acid Sequence In Humans (June 3, 2006)  

Single substitution discovered in current H5N1 was also found to be present in the last two major human pandemics of 1957 (H2N2) and 1968 (H3N2).

BOSTON (PRWEB) June 3, 2006 -- WHO and CDC spokespersons have recently announced that no significant worrisome sequence changes have been observed so far in H5N1 isolates from high mortality H5N1 Indonesian human cases (CIDRAP: Center for Infectious Disease Research and Policy News, May 24, 2006). Significant sequence changes are thought to be required for person-to-person transmission to occur, a necessary prerequisite for a human pandemic.

Using new search technology, FluForecast® software (see www.replikins.com for background and data), Replikins, Ltd. has discovered that in fact, a change in the amino acid sequence has occurred: a recent single amino acid substitution, to be referred to as "Sub", in an H5N1 virus protein, which may be significant because of the last time it was seen.

The company detected the amino acid "Sub" and tracked the sequence in which it occurred back 49 years. Sub is absent from all earlier H5N1 back to H5N1's first appearance in 1959, and is only present in the last two high-mortality influenza pandemics, of 1957 (H2N2) and 1968 (H3N2), which were responsible for millions of deaths, and in a recent, fortunately brief, outbreak of H7N7, with one human death. The company's FluForecast® software found the Sub amino acid substitution in earlier swine H1N1 infections, but not in recent chicken H5N1 isolates, and only in recent human H5N1 isolates, and only in human cases in areas with high mortality. Sub is present in isolates from Vietnam and Indonesia human H5N1 cases. This substitution correlates with epidemiological evidence that suggests that human person-to-person 'cluster' transmission may already have occurred, although infrequently to date.

Dr. Sam Bogoch, the company's chairman, said that the sequence in which Sub occurs is a small virus peptide which the company has found to be conserved in H1N1, H2N2, H2N3, and H5N1, for 88 years, from 1917 to the present. The company has also found that an increase in concentration of peptides of this type in proteins is associated with rapid replication and epidemics. With use of the company's FluForecast® software, for the first time, strain-specific quantitative protein correlations with epidemics have been observed. The rise in 'Replikin Count' (number of replikins per 100 amino acids), detected by the FluForecast software, has been found to be quantitatively correlated with and predictive in advance of the last three flu pandemics of the past century and the last three H5N1 epidemics from 1997 to the present.

FluForecast® permits advance strain-specific warning of 1 to 3 years that an epidemic or pandemic is on its way, thus allowing greater time and more specificity in tailoring more accurate, potentially safer, synthetic influenza vaccines. Previous lack of information of the substituted structure of H5N1, which might be the agent of the next pandemic, has hindered attempts to produce appropriate vaccines. In addition, current egg- and cell-based methods produce vaccines which contain thousands of unwanted proteins which may produce undesirable side effects, take 6 to 9 months or more to make, and more time to test. Replikins Ltd. is now synthesizing several new synthetic flu vaccines and conducting initial trials.

While a single substitution, alone, may not guarantee a pandemic, and the function of the substitution is not as yet known, the occurrence of the same substitution of amino acid "Sub", at least as a marker in the last two high-mortality pandemics, in 1957 and 1968, its occurrence now only in humans, accompanied by high Replikin counts and high mortality rates, together may suggest, in contrast to previous more comforting assessments, that H5N1 is indeed on the path to a human pandemic. What finally determines if and when a full-force pandemic materializes is still unknown. "Replikins is working with several government and private institutions to test the company's new synthetic vaccines" said Dr. Bogoch, Chairman of Replikins Ltd.

4. Replikins: Predicting global epidemics replication data
(May 4, 2006)  

Founded within the last month and based on technology aimed at predicting future epidemics, Replikins (Boston) has developed a software program for calculating the spread of influenza strains and is preparing to launch animal studies involving the first of its synthetic vaccines targeting the flu.

Work at the start-up firm focuses on its namesake, replikins, viral peptides that can be measured by their rate of replication to determine the potential of specific virus strains becoming global epidemics.

Although virus replication has been studied for 50-plus years, it's only recently that researchers have discovered the replikins, said company founder Samuel Bogoch, a former faculty member of Harvard and Boston University School of Medicine.

He said the find was "based upon the recognition of a chemical change, or peptide change, that occurs with rapid replication," and the ability to track those changes. Flu viruses were the first to be studied with the method, mostly because researchers were able to access epidemiological data from the Centers for Disease Control and Prevention (Atlanta) going back almost 100 years. Using Replikins FluForecast computer program, the company was able to analyze peptide sequences from those strains, which included the strain of H1N1 subtype that caused the Spanish flu pandemic of 1918. Analysis revealed that, prior to the outbreak, there was a strain-specific increase in replikin count.

"We had a chance to compare the absolute levels of the peptides in quantitative amounts to the occurrence of epidemics," Bogoch told Diagnostics & Imaging Week's sister publication BioWorld Today, "and we were pretty surprised to find that there's a point-to-point correlation between the high points of the epidemics" and high replikin counts.

The FluForecast program is designed to measure the peptide changes, which typically occur a year to three years before the epidemic itself, Bogoch said.

For example, the outbreak of severe acute respiratory syndrome (SARS) caused by a coronavirus, which appeared for the first time in 2003, could have been predicted using the technology, he said.

Because SARS had no data history, the company was not able to track the specific virus, but a look at the whole coronavirus group showed that the replikin count "stayed quite low in the dormancy area of 1 to 2 replikins per 100 amino acids" for several years before 2002 when it suddenly increased by three or four times that level, Bogoch said. "Then, in 2003, out pops the SARS epidemic."

The count fell again, and no case of SARS has been reported since 2003.

It's like a "factory" that is the busiest "before the product is released," Bogoch said, "which is good, because it gives us an opportunity we haven't had before - to see in advance of what's coming and to see it in quantitative terms."

The discovery is made even more poignant by the threat of a potential avian flu pandemic. Bogoch said the technology was able to predict three of the avian flu epidemics since they first emerged in Hong Kong in 1996-1997. Following early reports, Hong Kong officials were meticulous about destroying birds that could carry the virus, and the replikin count fell to normal levels in 1997, ending the threat, for a little while.

"They declared victory, but our replikin count said that it was back up again [in] 2002 and 2003," Bogoch said, adding that the count rose again before the virus emerged in Vietnam in 2004 and "since then, the replikin count has stayed up and hasn't gone down yet."

As far as whether this could signal a future pandemic, Bogoch said "we do not have any clue this is about to end."

Replikins was formed around the program, but predicting a potential pandemic is only the first step. In addition to counting replikins, the FluForecast technology also records which of the structures are most prevalent in any given strain, providing researchers with a specific target at which to aim a vaccine.

"So instead of going blind, you have a target [on which] to build your vaccine," Bogoch said.

He added that the company also works with synthetic vaccines to avoid the chance for protein contamination that comes from using part or all of the actual virus to synthesize a treatment. One of the most notable instances of contamination occurred in 1976, when people were "rushing to get inoculated for the swine flu epidemic," before the vaccination program was cancelled after 25 deaths and a rise in Guillain-Barre syndrome were linked to the vaccine, he said.

With a synthetic vaccine that's targeted to specific amino acids, "we have a better chance of knocking out the organism, and there are no contaminants," Bogoch said.

At this time, the company is "about halfway there," he added. "We know the [vaccine] works to make antibodies, but the question is does it protect against [the virus]?"

To answer that question, Replikins is preparing to begin preclinical trials in several countries to test the vaccine technology in animals. If the results are promising,

The company's FluForecast also could help government's predict which seasonal flu strain is most likely to hit in the coming years to make sure vaccine stockpiles include the most effective vaccines.

Beyond influenza, Replikins anticipates using its program for measuring rapid replication to address other infectious diseases such as AIDS, foot-and-mouth disease, and malaria.

The company recently completed its first financing, which Bogoch described as "very generous." It has a "handful" of employees, with expectations of hiring additional staff to set up labs in areas outside the U.S.

"We'll be very busy in the coming year," Bogoch said, "testing as many of these diseases as possible to see if we get good antibody responses to our vaccines based on the replikin structure."

3. FluForecaster Firm Born (April 28, 2006)  

Replikins Ltd., a new Boston company headed by a venerable biochemist who has mined both data and his own experience, is developing predictive software and a possible vaccine.

The enterprise -- founded by 78-year-old Samuel Bogoch -- is rolling out FluForecast, its software designed to analyze data to predict when certain infectious diseases will "replicate" and reappear, such as the much-publicized Avian flu. Replikins will market it as a service to governments and life-sciences companies attempting to predict such threats, while its vaccine would counteract those threats.

Bogoch, a founder of the neurochemistry laboratory at Harvard Medical School and a former faculty member at Boston University School of Medicine, launched the company with his wife and colleague, Eleanor. Bogoch said he raised "more than $10 million" in preparation for incorporation, but he declined to identify investors.

"Everyone is concerned about epidemics, and people say I am a Johnny-come-lately," said Bogoch. "but I have been working on this stuff since I got my Ph.D. from Harvard in 1957."

The project involves animal testing at sites worldwide. The startup focused first on the influenza virus and is developing a vaccine to counter the virus. In developing its software, Replikins used data from the Centers for Disease Control going back to 1918, the year of one of the most deadly influenza outbreaks in history.

"We discovered a pattern of the same peptides in virus outbreaks," said Bogoch. "After that, we developed the software to study the replikins quantitatively to give advance warning for the first time of virus outbreaks and dormancy."

The company has worked with both the CDC and the National Institutes of Health on developing data, but it is not supported by those agencies. Carl Franzblau, chairman of the department of biochemistry at Boston University School of Medicine, said he worked with Bogoch in the 1980s and early 1990s.

"I don't know his new company, but I remember him as a fine scientist who did some very elegant biochemistry," said Franzblau. "He made discoveries from the time he left graduate school, and has done much good work since."

2. Virus Replication Discovery Helps Predict Epidemics
(April 24, 2006)  

Replikins, Ltd. has discovered of a group of virus peptides that predict whether a virus is rapidly replicating and whether it is likely to spread. The company has designed software which can now detect and count these proteins which ma protein or other biological phenomenon has been known to correlate with viral epidemics. Researchers have had no objective quantitative protein based means to predict if, and what, strain of a given viral organism will become a public health threat. The current concern over when, or if, there will be an avian flu epidemic has drawn attention to the need for improved measures to help predict, prevent and prepare for emerging health threats.

"We have identified a group of viral peptides we call 'Replikins' whose concentration correlates with rapid viral replication, and can give advance notice of virus epidemics," said Samuel Bogoch, M.D., PhD, a former faculty member of Harvard and Boston University School of Medicine who with his wife and colleague Dr. Elenore Bogoch discovered this new group of peptides.

Groups of Replikins can now be categorized and counted, using computerized software programs, providing a forecasting method. The FluForecast(TM) program analyzes the peptide sequences of a virus and can indicate by the virus's strain-specific Replikins concentration in viral proteins which strains are replicating rapidly, thereby creating the potential for an epidemic. The FluForecast(TM) program has quantitatively analyzed historical data on Replikins (from 1917 to the present) in protein sequences in strains of influenza viruses saved by agencies such as the World Health Organization and The U.S. Centers for Disease Control and Prevention. The FluForecast(TM) program has shown that higher concentrations of Replikins correlate with the emergence of epidemics and lower concentrations of Replikins correlate with dormancy in the three great flu pandemics of the past century and in the H5N1 outbreaks of recent years (see data in Figures 1 and 2 attached below).

Replikins' structures have been found to be conserved both intrastrain and interstrain for as long as 87 years, based on data going back to the 1917-18 flu pandemic. Some Replikin structures appear for only one or a few years, but some persist, that is are conserved for decades. In 2002 Replikins scientist Dr. Bogoch did a Replikin analysis of the published partial sequence of the 1917 influenza virus isolated from a goose and the sequence of the influenza virus that caused the 1918 human influenza pandemic. Dr. Bogoch showed that the structures, (Replikin structures) of the bird and human influenza strains were closely related and concluded that the pandemic of 1918 derived from this 1917 sequence of the bird flu.

Dr. Bogoch's assertion was confirmed in a recent Nature article of 2005. The conservation of Replikin structures as identified by the FluForecast(TM) program creates a more constant target for the development of vaccines to prevent future contagious outbreaks. In explaining how the Replikins proteins were identified Dr. Bogoch, who founded the Neurochemistry Laboratory at Harvard Medical School, said, "We initially looked at rapid cell replication in tomato gemini virus, which causes great losses of tomato crops, and at other infectious diseases. We searched for similarities between viruses and bacteria, which can duplicate rapidly. For example we found that the slowly replicating HIV virus has a Replikin Count(TM) peptide quantity of 1.1 and the rapidly replicating HIV virus has a Replikin Count(TM) peptide quantity of 6.8. We first focused on the influenza virus, because the C.D.C. has epidemiological data available going back nearly 100 years, and we discovered a pattern of the same peptides in virus outbreaks.

"After that, we developed the software to study the Replikins quantitatively to give advanced warning for the first time of virus outbreaks and dormancy. In addition, Replikins provide novel targets for future antiviral agents." This Saturday, April 22nd, Replikins and the FluForecast(TM) program will be discussed and demonstrated in Boston at a meeting at Replikins, Ltd., 38 The Fenway, Boston at 10:30 am. The company recently closed a significant round of financing to introduce the FluForecast(TM) program and Replikins technology. Additional information is available at http://www.replikins.com. Replikins, Ltd. http://www.replikins.com

1. Replikins, Ltd. has discovered a group of virus peptides that predict whether a virus is rapidly replicating and whether it is likely to spread. (April 21,2006)  

The company has designed software which can now detect and count these proteins which may allow scientists to better predict viral epidemics, such as the H5N1 (avian) flu.

To date, no protein or other biological phenomenon has been known to correlate with viral epidemics. Researchers have had no objective quantitative protein based means to predict if, and what, strain of a given viral organism will become a public health threat. The current concern over when, or if, there will be an avian flu epidemic has drawn attention to the need for improved measures to help predict, prevent and prepare for emerging health threats.

"We have identified a group of viral peptides we call 'Replikins' whose concentration correlates with rapid viral replication, and can give advance notice of virus epidemics," said Samuel Bogoch, M.D., PhD, a former faculty member of Harvard and Boston University School of Medicine who with his wife and colleague Dr. Elenore Bogoch discovered this new group of peptides.

Groups of Replikins can now be categorized and counted, using computerized software programs, providing a forecasting method. The FluForecast(TM) program analyzes the peptide sequences of a virus and can indicate by the virus's strain-specific Replikins concentration in viral proteins which strains are replicating rapidly, thereby creating the potential for an epidemic. The FluForecast(TM) program has quantitatively analyzed historical data on Replikins (from 1917 to the present) in protein sequences in strains of influenza viruses saved by agencies such as the World Health Organization and The U.S. Centers for Disease Control and Prevention. The FluForecast(TM) program has shown that higher concentrations of Replikins correlate with the emergence of epidemics and lower concentrations of Replikins correlate with dormancy in the three great flu pandemics of the past century and in the H5N1 outbreaks of recent years (see data in Figures 1 and 2 attached below).

"Combined with the software that analyzes viral strains, we now -- for the first time -- have an objective means of determining the threat level of a virus," said Dr. Sam Bogoch. "To our knowledge, there is no other product which provides this predictive information."

Replikins' structures have been found to be conserved both intrastrain and interstrain for as long as 87 years, based on data going back to the 1917-18 flu pandemic. Some Replikin structures appear for only one or a few years, but some persist, that is are conserved for decades. In 2002 Replikins scientist Dr. Bogoch did a Replikin analysis of the published partial sequence of the 1917 influenza virus isolated from a goose and the sequence of the influenza virus that caused the 1918 human influenza pandemic. Dr. Bogoch showed that the structures, (Replikin structures) of the bird and human influenza strains were closely related and concluded that the pandemic of 1918 derived from this 1917 sequence of the bird flu. Dr. Bogoch's assertion was confirmed in a recent Nature article of 2005. The conservation of Replikin structures as identified by the FluForecast(TM) program creates a more constant target for the development of vaccines to prevent future contagious outbreaks.

In explaining how the Replikins proteins were identified Dr. Bogoch, who founded the Neurochemistry Laboratory at Harvard Medical School, said, "We initially looked at rapid cell replication in tomato gemini virus, which causes great losses of tomato crops, and at other infectious diseases. We searched for similarities between viruses and bacteria, which can duplicate rapidly. For example we found that the slowly replicating HIV virus has a Replikin Count(TM) peptide quantity of 1.1 and the rapidly replicating HIV virus has a Replikin Count(TM) peptide quantity of 6.8. We first focused on the influenza virus, because the C.D.C. has epidemiological data available going back nearly 100 years, and we discovered a pattern of the same peptides in virus outbreaks.

"After that, we developed the software to study the Replikins quantitatively to give advanced warning for the first time of virus outbreaks and dormancy. In addition, Replikins provide novel targets for future antiviral agents."

This Saturday, April 22nd, Replikins and the FluForecast(TM) program will be discussed and demonstrated in Boston at a meeting at Replikins, Ltd., 38 The Fenway, Boston at 10:30 am. The company recently closed a significant round of financing to introduce the FluForecast(TM) program and Replikins technology. Additional information is available at http://www.replikins.com/.