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H5N1 Indonesian Pandemic Vaccine Sequence Released

Recombinomics Commentary
March 26, 2006

The human H5N1 sequence selected for the next US pandemic vaccine target was just released at Los Alamos (A/Indonesia/5/2005).  It is from the father of the index case in Indonesia.  Samples from the index case and her sister were not collected, but H5N1 was isolated from her father.  Media reports of the familial cluster were in mid-July,  and the sequence sof the HA and NA were deposited at Los Alamos by the CDC on August 1. 2005 at 9:29 GMT.  The sequence was just updated and released to the public, although the other 6 gene segments are still locked up in the password protected side of the database, along with dozens of other H5N1 sequences from around the world.

Although the sequence is most closely related to Indonesian poultry, especially A/chicken/Wajo/BBVM/2205, there are many polymorphisms not in the most closely related sequence.  Moreover, at the protein level there are human specific changes not found in the database, including a new glycosylation site, A90T, as well as a novel cleavage site RESRRKKR.

Many other changes are in the sequences and these polymorphisms are easily linked to H5N1 sequences in the area or in a range of migratory birds.  There are polymorphism found in Vietnam and not Thailand as well as Thailand and not Vietnam.  There are sequences in the migratory ducks from Jiangxi that appeared at Qinghai Lake and sequences that did not.  There are Qinghai sequences not in  the Jiangxi ducks and sequences from Henna tree sparrows and Hunan blackbirds.  There are a few polymorphisms not limited to H5N1 isolates, including the recent Bavarian mallard sequence or the Canadian or Spanish swine.

In short, the Indonesian sequence is a genetic passport of where sequences have recombined to produce a rapidly evolving deadly H5N1 in Indonesia in July of 2005.  The more recent infections no doubt have sequences that have evolved significantly since July of 2005 because of the large number of sequences flying into Indonesia as well as the sequences in people, pigs, and poultry resident within Indonesia.

This genetic soup is getting thicker as Indonesia fails to test and cull and WHO keeps the evolving story under lock and key, available to its consultants who have yet to issue any public statement acknowledging that H5N1 is rapidly evolving via recombination.  Instead they issue press releases about reassortment and random mutations and chase the evolving H5N1, which is no contest with current approaches.

It is long past time to release the data.  All 8 gene segments of the first official H5N1 case in Indonesia should have been released in August, 2005 and the locked up sequestered sequences should be released immediately.

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