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H1N1 Evolution Outpacing Vaccine and Host Defenses
Recombinomics Commentary 13:32
November 30, 2009

The designation of one of the Ukraine D225G isolates as a "low reactor" raises concerns that the H1N1 evolution is outpacing the vaccine as well as immune responses from unvaccinated hosts.  This concern was present ealry when changes began to appear at position 225, a known antigenic site.

One of the highest profile isolates was the San Francisco traveler to Hong Kong, who was reported (in July)  to have Tamiflu resistant H1N1, even though she had not taken Tamiflu. Her case was mild and she recovered without antiviral treatment, but the virus had a receptor binding domain change, D225E.   A survey of D225E at the time demonstrated that it was first reported in the US in New Jersey, but not subsequently.  However, it had spread to many other countries, raising concerns that the US surveillance was missing this widespread sub-clade.

Moreover, there were soon examples of D225G and D225N in other early samples supporting the use of position 225 to escape host defenses.  The concern of multiple changes at the same position increased when sequences from fatal cases in Sao Paulo were releasd recently.  The July/August collections had D225G in two of two fatal cases, and D225N in two of two other fatal cases, with 3 of 4 samples coming from lung.

These concerns increased when sequence data from Ukraine was released and 4 of 4 fatal cases had D225G.

The above data reinforced concerns that the changes at position 225 were becoming more prevalent, especially in samples collected from affected organs of fatal cases.

The concerns ratcheted up another notch when one of the four cases was characterized antigenically, and was reported to be a "low reactor".  Since the low reactor had only one amino acid change in HA, the role of D225G in the reduced titers raised the level of concern higher.

However, WHO has yet to address this result.  The "low reactor" status was quietly added to the characterization sheet at GISAID and there has been little comment in the mainstream media, other than a sentence in the New York Times on Friday.

Comment form WHO and other agencies, including Mill Hill and the CDC, who were conducting testing of the Ukrainian samples, is long overdue.

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