Commentary
Accelerated
H1N1 Tamiflu
Resistance Via Vaccine Mismatch
Recombinomics Commentary
23:11
March 25, 2009
Also included are isolates from Japan that were associated with an elementary school in the fall, which matches the dominant H1N1 sub-clade in the US. HA sequences from these isolates have A1893T with G189V and H196R.
Japan NIH also released titers of 18 isolates against ferret reference anti-sera. These data clearly demonstrate significant drift of the recent isolates from last year’s H1N1 vaccine target, A/Solomon Islands/3/2006 (clade 2A). However, last season there was little clade 2A in circulation, raising concerns that the drift was accelerated by a poorly matched vaccine. Although the 18 test antigens represented multiple recent sub-clades, with HA sequences with A193T plus one or two additional changes at flanking positions 187, 189, and 196, all had reductions in titers when tested with the clade 2A reference anti-sera. Two were reduced four fold, but the remainder had reductions ranging from eight to thirty-two fold.
Similar results were generated for clade 2C, which was represented by recent anti-sera against A/Shiga/8/2008. One isolate was reduced four fold while the rest were reduced eight to thirty-two fold. These lower titers help explain the spread of clade 2B in Asia, where clade 2C was widespread last season.
However, reduced titers were also seen for A/Brisbane/59/2007 (clade 2B), although results were more complex. Two reference sera were used. One was directed against Brisbane/59 grown in eggs and like last season, the anti-sera had significant cross reactivity with the reference sera as well as the recent isolates. The mammalian cell isolate however discriminated between the reference sera, especially for clade 2C, where the titer was reduced eight fold. This level of reduction was also seen for four of the test isolates. Three were the dominant sub-clade in Japan, while the other was the dominant sub-clade in the US. These titer reductions support reports of vaccine failures in Asia and North America.
The recent announcement that the H1N1 target for the 2009/2010 will remain unchanged raises concerns of more vaccine failures next season.
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