Commentary
Emergence of Vaccine and Tamiflu Resistant H1N1
Recombinomics Commentary 23:15
February 18, 2009
The above comments from Italy's weekly influenza report , indicate that the vaccine and Tamiflu resistant H1N1 isolates (A/Parma/23/2009, A/Parma/24/2009, A/Parma/25/2009, A/Parma/26/2009) match recently released US sequences, A/Wisconsin17/2008 and A/Washington/8/2008. The HA sequence for both isolates have the same three changes (A193T, G189A, S145N using H3 numbering). Moreover, the two changes flanking the receptor binding domain, G189A and A193T are in A/Hawaii/19/2008, and A/Mbagathi/7586/2008, as well as the recently released A/Philippines/1159/2008. Moreover, phylogenetic analysis of the NA sequences predict these changes will also be in Japan isolates, Miyagi/35/08, Yamaguchi/26/08, Yamaguchi/27/08, Yamaguchi/28/08. Both Japan and South Korea have had explosions of H1N1 Tamiflu resistant cases, suggesting that the vaccine resistant H1N1 is widespread.
The A193T is in all public H1N1 Tamiflu resistant sequences in the United States and is now also in all public isolates in Spain, and the vast majority if not all isolates in Japan. Although A193T was also linked to the fixing of Adamantane resistance in H1N1 clade 2C as well as Tamiflu resistance in H1N1 clade 2B, it is not in the current vaccine for the northern hemisphere in 2008/2009, and is not vaccine for the southern hemisphere in 2009, nor the northern hemisphere in 2009/2010.
The absence of these important changes in seasonal flu vaccine targets remain a cause for concern.
In Italy, three of the first five H1N1 isolates were from patients who had taken this season's vaccine, suggesting the H1N1 was not only Tamiflu resistant, but also vaccine resistant. Similarly, a report from Taiwan cited vaccine resistance levels at 70% for H1N1, and Japan also reported lower titers for H1N1 isolates when compared to the Bisbane/59 isolate used to represent H1N1 in the current vaccine.
Similarly, both South Korea and Japan reported explosions of cases linked to H1N1 and recently released sequences in the United States have the same three acquisitions reported in Spain. Moreover, recent weekly reports from the CDC do not show a reduction in the levels of H1N1. The vast majority of influenza in the US is influenza A, and the vast majority of influenza A is H1N1, with Tamifu resistance levels approaching 100% (the few sensitive isolates appear to be clade 2C).
Thus, the current approach of using vaccines to chase viral evolution continues to be a cause for concern. The fixing of H274Y in H1N1 seasonal flu raises serious concerns about the potential use of Tamiflu in an H5N1 bird flu pandemic.
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