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H1N1 S188T Low Reactors In Germany
Recombinomics Commentary 18:00
February 1, 2011

Mill Hill has released another series of recent H1N1 sequences at GISAID.  Included were six sequences from three locations in Germany (Nordrhein-Westfalen, Berlin,Baden-Wurttemberg).  All six have S188T (see updated list here), but represent different sub-clades with the S188T sub-clade.  Remarkably, 5 of the 6 have one or more changes at positions 156, 157, or 158.

This region produces low reactors, which are characterized by a drop in titer of four fold or more.  Two of the first designated low reactors in 2009 were from Germany, and both had G158E.  One was designated as a low reactor by Mill Hill and the other was designated as a low reactor by the CDC.  Although subsequent isolates from the US which had G158E were not designated as low reactors by the CDC, all US low reactors had a change at position 159.  Similarly, an isolate from Kenya, which was a mixture at position 158 (G158E plus wild type), also had S188T and was designated as a low reactor, which was true for an isolate from India with S188T and S186P.

Although Mill Hill has not released antigenic characterization data on these recent (all were collected in late December, 2010) isolates, the presence of changes at positions 156, 157, and/or 158, coupled with S188T will almost certainly produce a low reactor designation.

The fixing of S188T (as seen in the above list, S188T is also in recent sequences from Madagascar, Egypt, Latvia) strongly suggests acquisition of S188T facilitates the evasion of prior immune responses to pandemic H1N1 infections or vaccinations.

The presence of these additional changes at positions 156, 157, or 158 in 5 of 6 recent isolates from Germany incates H1N1 is rapidly evolving away from the 2009 immune responses and raises concerns about the continued use of California/07/2009 as an H1N1 vaccine target.

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