Replikins' FluForecast Software Pinpoints Change in Deadly Bird Flu Amino Acid Sequence In Humans

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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).

Replikins is working with several government and private institutions to test the company’s new synthetic vaccines

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 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.


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Carol Zepp
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