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Commentary
WHO Approves H1N1
Vaccine Inventory Control
Recombinomics
Commentary 13:38
February 18, 2010
The above comments on the WHO recommendations for composition of the 2010/2011 vaccine suggests that the California/7 target used in the current killed pandemic vaccine will be used in the northern hemisphere 2010/2011 season as well as the 2010 season for the southern hemisphere, even though the target does not have D225G, and has five additional differences with the current consensus sequence of H1N1.
The recommendation was not a surprise. Seasonal H1N1 has all but disappeared, and the new recommendations for the northern hemisphere match the current recommendations for the southern hemisphere, allowing for seamless production between seasons, and inventory control for excess California/7/2009 not used in the current season.
The recommendation was telegraphed by the WHO report on D225G, which was largely a whitewash to allow for continued use of California/7/2009 which was originally a mixture for D225G and Q226R. The target selected for the killed vaccine, X-181A, has Q226R and does not have D225G. It also has four additional differences, raising concerns regarding matches between the vaccine target and most H1N1 isolates.
Antigenic testing has indicated that these differences have not generated a 4 fold or more reduction in reference ferret anti-sera. However, an isolate from Ukraine, A/Lviv/N6/2009 was antigentically characterized by Mill Hill, who designated the isolate a “low reactor”. The CDC isolated a clone with the same sequence, yet designated as California/7-like, indicating the titer had not been reduced by four fold or more indicating the assay could produce a significant difference due to testing procedures or reference anti-sera.
These types of discrepancy have appeared previously. In the 2006/2007 the target for the H1N1 seasonal flu was A/Solomon Island/3/2006, but at the start of the season in the northern hemisphere Solomon Island/3 (clade 2A) had been replaced by Brisbane/59-like (clade 2B) and Hong Kong/2346-like (clade 2C), but all were considered a “match” based on reactivity with ferret anti-sera. However, it soon became clear that the cross reactivity was based on how the virus was grown prior to immunizing ferrets, and when the isolation procedure was changed, new anti-sera readily distinguished between clade 2A, clade 2B, and clade 2C, and the following year Brisbane/59 (clade 2B) was selected as a target that better represented the sub-clades in circulation.
This season the discrepancy is with D225G, and since California/7 isolates have been generated with D225G as a mixture, wild type D225, and D225G, the selection of target for ferret anti-sera, as well as the current vaccine (the live attenuated vaccine target does have D225G), could significantly impact the specificity of the resulting immune response.
The association D225G/N with fatal H1N1 cases and the increase in release of sequences with D225G/N has raised concerns that the current vaccine, as well as the response to wild type H1N1 leads to selection of D225G/N, which may then be circulating at a higher frequency in a third wave in the northern hemisphere this season, or in the upcoming seasons in the southern hemisphere and northern hemisphere. The current WHO recommendations allow for use of current inventory of California/7, that does not include D225G, raising concerns about the future utility of the newly selected target.
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