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Commentary
All CDC Designated US pH1N1 Low Reactors Have Same Change
Recombinomics
Commentary 17:17
April 7, 2010
The above comments from the latest CDC weekly update describe five low reactors in the United States. The first two (A/South Carolina/18/2009 and A/Utah/20/2009) had N159D, suggesting this position played a role in the CDC designation.
The CDC has released another series of sequences at GISAID, including 83 patients from the US. Most were from the end of 2009 or beginning of 2010 (44 were from 2010). These sequences included three designated low reactors, and they also had changes at position 159 (N159K or N159S), suggesting the anti-sera used by the CDC for antigenic characterizations is tightly linked to position 159 changes. The three designated isolates were A/Texas/76/2009, A/New Mexico/16/2009, A/Michigan/29/2009.
In addition to the above designated low reactors, A/New Mexico/15/2009 and A/New Mexico/16/2009 where not characterized, but also have N159S. Similarly a sequence at Genbank, A/Wisconsin/629-DO1935/2009, has N159K and sequences generated by the Air Force also have N159K, A/OCONUS4/4081/2009, or N159S, A/Texas/732/2009.
Earlier, the CDC had designated A/Bayern/69/2009 a low reactor, which had G158E. Mill Hill had designated another isolate, A/Bayern/62/2009, a low reactor, and it also had G158E. This change is adjacent to the position 159 changes, as well as position 157 changes, which were found in pH1N1 escape mutants, indicating all three positions, which were in the same antigenic site, could significantly impact neutralizing antibodies.
However, subsequent G158E isolates in the US were not designated low reactors by the CDC, suggesting a change in the CDC’s antigenic assay. Mill Hill also designated D225G as a low reactor, although the CDC did not.
As noted above, the CDC only claims 5 low reactors in the US and all 5 have changes at position 159, raising more questions about the sensitivity of the CDC assay. The selection of California/7/2009 as the vaccine target was controversial, because it has five non-synonymous differences with the pH1N1 consensus sequences, so one or two additional changes could create low reactors and vaccine failure.
The failure of the CDC to find low reactors that do not have a position 159 change is cause for concern.
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