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Chihuahua H1N1 LOW REACTOR In Alaska
Recombinomics Commentary 23:55
August 17, 2011

The CDC recently released a Chihuahua sub-clade sequence, A/Alaska/14/2011, which they designated a LOW REACTOR (at GISAID).  The HA sequence (from 41M collected March 30, 2011) had a mixture at position 159 (N159D and N159E) and both changes have been noted in other low reactors.  In the 2009/2010 season all five US H1N1 sequences designated as low reactors by the CDC had a change at position 159.

The sequence was closely related to another Chihuahua sequences from Alaska, A/Alaska/12/2011, which was collected 6 days later from a child (12M), raising the possibility that cases were linked.  Both sequences were deposited June 21, but the release of the low reactor sequence was delayed almost two months (released August 15) for unknown reasons.  However, the sequence similarities and collection dates raise concerns that N159D and N159E are also present in the latter collection, but not detected.

The failure to identify changes at positions 156-159 has becme an issue after the CDC complained about other WHO labs (Mill Hill in the UK, NIID in Japan, WHO regional center in Australia) were finding too many changes at these positions because they didn’t use “normal” MDCK cells.  Changes at these positions create LOW REACTORS like the CDC designated sequence above, but the CDC identified a very low number of such cases (as noted, in 2009/2010 no US isolates without a change at position 159 were designated as low reactors).

The absence of low reactors led to the unanimous decision to leave all three vaccine targets unchanged for the 2011/2012 season.  However, the CDC and WHO region center have recently begun testing new candidates (three for influenza B, three for seasonal H3N2, and two for pandemic H1N1.  For pandemic H1N1, both candidates have Q226R, although A/South Carolina/02/2010 and A/Victoria/502/2010 have representations without Q226R (egg isolates of Victoria/502/2010 have D225G).  In addition to the receptor binding domain changes, the US vaccine target, A/South Carolina/02/2010, also has K157E, even though the original sequence was wild type.  The inclusion of K157E and Q226R in the new H1N1 vaccine targets raises concerns that these levels of these LOW REACTOR changes or receptor binding domain changes are markedly higher than the levels indicated in the sequences from H1N1 grown on “normal” MDCK cells.

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