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Commentary

CDC Identifies 2012 H3N2 Low Reactors In United States
Recombinomics Commentary 12:30
March 20, 2012

A/California/7/2009 (H1N1)pdm09-like virus
A/Victoria/361/2011 (H3N2)-like virus
B/Wisconsin/1/2010-like virus

The above isolates are the vaccine targets for the 2012/2013 season for the northern hemisphere.  The H3N2 target was changed from A/Perth/16/2009 which showed a 16 fold reduction (from 2560 to 160) when tested against A/Victoria/361/2011, as demonstrated in table 2 of the February.2012 WHO vaccine update.

This significant drop in titers is linked to the dramatic increase in low reactors reported by the CDC from week 8.  At that time the CDC had released 22 H3N2 sequences from 2012, but none were designated as low reactors (only 1/3 had been tested).  The antigen characterization data was recently updated, which include the designation of 7 H3N2 isolates from 2012, and 5 of the 7 represented the same sub-clade, which has a number of non-synonymous changes, including A198S and V223I, both of which are also in A/Victoria/361/2011 (collected in late 2011), the new H3 vaccine target.

In addition to the 5 isolates listed as LOW REACTORS, 10 additional isolates mapped as the same sub-clade.  Thus, 15/22 of the January 2012 isolates (collection dates through January 23) were the same dominant sub-clade that is represented by the new target, and was widespread worldwide in January (se list of GISAID sequences with V223I or A198S).

Thus, the dominance in January 2012 in the US suggests that the vast majority of February 2012 H3N2 cases in the United States would be low reactors with the two receptor binding domain changes cited above.  However, the CDC update on the Maryland death cluster indicated the sequence data supported recognition by the 2011/2012 vaccine, which used Perth/16 as the H3N2 target, which had a 16 fold reduction in titer when tested against Victoria/361.

Release of the sequences from the Maryland death cluster would be useful.

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