2010-08-31

HA 230I RBS Polymorphism Potential for Europe

Current trending indicates a reportable potential for the M230I polymorphism spreading on the Hemagglutinin of PF11. This Receptor Binding Domain change may enhance Vaccine Escape from the currently selected vaccine target candidate, CA/07 X181. 

For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I.  Model adjustment and data transparency allowed a second set of detailed geographic predictions on 2010-08-09 that have also found traction.

The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248.  89% of the amino acid positions have notated revisions.

Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data.  The GeneWurx model approximates that HA 230I will appear in the PF11 RBS according to the following geographic probabilities.

  • 75% probability in Germany sampled by 2010-12-01.
  • 75% probability in Spain sampled by 2010-12-01.
  • 85% probability sampled by 2010-12-01 in one of:
    • Denmark
    • Norway
    • Sweden
  • 5% or less probability of HA 230I within 60 days of conserving across PF11.
  • 7% probability of HA 230I within 180 days of conserving on one or more Hydrae.
This HA polymorphism guided an investigation suggesting that  anti-viral resistance from the NA H275Y revision is not the only genetic concern with over-usage.  Anti-viral drug usage may drive 230I genetic acquisition, with a higher potential among children and young adults (0-24 years old). The sparsity of complete sequences, discounted by the lack of required meta-data, allows only a rough postulation on the mechanism.

An accelerated viral self-revision, subsequently moving toward M230I, may be modulated by the substantially higher rates of host exposure in the lower age brackets. Additionally, that group’s multiplicity of exposure to a wider variation of influenza strains may factor into the host response/viral revision equation. In plain terms, the viral reservoir is being forced toward hard labour in order to infect and re-infect the youth.

Just as hard work builds muscle, viral exertion against a complex host response challenges the reservoir subset to revise toward an optimal solution. 230I is an excellent and proven tertiary response for a virus on this type of offensive.

These probabilities will be updated as additional data is made public.  Transparency at this post-pandemic stage is essential to formulate viable responses for the risk groups.  Release of sequences and clinical data of a finer detail and higher quantity will allow information-based decisions.



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