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D225G Evades Immune Response
Recombinomics Commentary 08:18
November 27, 2009

Antigenic characterisation: A/California/7/2009 like. Low reactor

The above comment is from the updated characterization sheet for A/Lviv/N6/2009, one of the four isolates from fatal cases in Ukraine.  All four isolates had D225G, and in the above isolate that was the only non-synonymous change in HA, indicating the polymorphism was escaping from the immune response.

D225G is in the receptor binding domain and therefore at the surface of HA, and several different polymorphism were noted at that position (D225G, D225E and D225N) suggesting the changes were to escape from the immune response.  Moreover the change was appearing on multiple different genetic backgrounds. This is not surprising, since position 225 is in an antigenic site and D225N was linked to the establishment of S31N in the H3N2 population.

However, this low reactor status is in marked contrast to earlier studies on vaccine target clones, which indicated D225G produce no difference in titer, highlighting the vagaries of reference anti-sera data.

This escape could also explain the increases in reported D225G cases as well as increases in hospitalizations and death.

More information on the discrepancy in results from two reference anti-seras would be useful.

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