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CDC Selects New H3N2v Pandemic Vaccine Target
Recombinomics Commentary 21:45
January 23, 2012

The CDC has selected a new H3N2v vaccine target, A/Indiana/10/2011 X203, as indicated by reassortant sequences released at GISAID in association with the New York Medical center in Valhalla, New York.  The target is a 5:3 reassortant with H3, N2, and PB2 from the target, which was isolated from an infected veterinarian (59M) from Indiana. 

The above three genes match the lineage for the first 10 H3N2v cases in 2011, in contrast to the earlier target, A/Minnesota/11/2010, which was from the index case of the Minnesota cluster.  The H3 matches the lineage in the trH3N2 cases in 2010, which were a precursor to the 2011 cases.  However, the N2 was a different lineage than the N2 in the first 10 cases in 2011, which were formed by a ressortment with the human 2010 trH3N2 sequences and an H1N2 sequence that matched the swine isolate from Ohio, A/
swine/Ohio/FAH10-1/2010.  However, the cluster from West Virginia has yet another N2, which, like the above isolates traces back to human N2 from 2003 H3N2, but is a lineage that evolved in trH3N2 swine isolates, in contrast to the new vaccine target, which evolved in trH1N2 swine isolates.  Moreover, the N2 in the West Virginia cluster is a recombinant with seasonal H3N2.

Thus, the new target is a closer match to the first 10 H3N2v cases in 2011, but does not match the largest cluster, which included two isolates, A/West Virginia/06/2011 and A/West Virginia/07/2011, as well as 22 contacts with ILI symptoms who were not tested.

However, the choice of H3N2v targets appears to be limited, based on the lack of sequences from isolates from the 3 cases in Pennsylvania, A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011, the 2 cases from Maine, A/Maine/06/2011 and A/Maine/07/2011, and the two West Virginia isolates listed above.
The failure to obtain viral isolates from the above samples is likely due to low RNA levels, which may be limited due to cross reactive immune responses directed against seasonal H3N2.  Low RNA levels is likely limiting detection of new cases because many are mild and without medical examination / testing, while others will be misdiagnosed as seasonal H3N2, as seen in the second isolate from Maine.

Thus, the level of H3N2v in circulation is likely several orders of magnitude higher than the 12 confirmed cases, raising concerns that the two constellations of H3N2v identified in 2011 may be poor representations of the H3N2v silently spreading, which may limit the utility of the vaccine based on the new target.

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