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Withheld 2011 H1N1 US Sequences Raise Pandemic Concerns
Recombinomics Commentary 15:30
March 28, 2011

The H1N1 influenza outbreak that affects the state of Chihuahua originated in Texas and New Mexico, said yesterday the governor Cesar Duarte Jaquez.

"It is confirmed that the lady who died recently in capital Chihuahua came from a Texas trip, just as those who are infected in Ciudad Juárez are all related to a trip to the United States, or have had contact with U.S. citizens "he said. 

The above translation on relationships between the H1N1 outbreaks in northern Mexico and the United States raise additional concerns about the 2011 sequences in the United States and the delay in release by the CDC.  Recently the CDC has been releasing series of H1N1, H3N2, and influenza B sequences almost simultaneously.  Last week H3N2 and influenza B sequences from 2011 collections were released, but H1N1 sequences have been withheld.  The last CDC release was February 2, 2011 and most released sequences were from December, 2010.  The recent evolution of H1N1 in the United States is not public. 

These sequences and antigenic characterizations were known prior to the recent decision to leave the 2011/2012 vaccine targets for the northern hemisphere unchanged, even though death rates are at historic highs and multiple reports on vaccine failures have been published.
The sequences from late 2010 were dominated by the sub-clade with S188T, which was also linked to vaccine failures.  Similar changes flanking position 190 were also seen in the 2009/2010 northern hemisphere season which led to vaccine failures of seasonal H1N1, which was also associated with the fixing of Tamiflu resistance (H274Y).

The vaccine target selection is heavily dependent on antigen characterization tests with are insensitive and unreliable.  These fatal flaws are most striking in seasonal and pandemic H1N1.  The lack of sensitive led to a limited number of low reactors last season in US isolates (all were limited to changes at position 159).  This low sensitivity is also present in the CDC FluView, which cites only one low reactor in the 2010/2011 season, even though most sequences have S188T which is linked to low reactor status. One isolate, A/Kentucky/09/2010 had three changes linked to low reactor status (G158E, S188T, and D225G) but was not designated as a low reactor by the CDC.

In addition to vaccine target selection, the sequences are important for monitoring H1N1 evolution, including receptor binding domain chnages.  Recent swine sequences from the US and elsewhere, including England and South Korea, signal extensive reassortment between triple reassortants (H1N1, H1N2, H3N2), and pandemic H1N1, which is also a triple reassortant.  These combinations involve genes with a long history of transmission in humans, raising concerns that H1n1 variants could again jump from swine to humans, which is most likely to happen at the present time, as happened in 2009 when seasonal flu levels decline.

Thus, the withholding of H1N1 from 2011 isolates in the United States increases pandemic concerns.

Sequences from the United States, Mexico, and Venezuela should be released immediately.

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