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CDC Testing New H3N2 Vaccine Target
Recombinomics Commentary 15:00
January 4, 2013

The early start of the flu season in general, and the dominance of H3N2 in northern regions of the United States, as well as Canada, has raised concerns that the 2012/2013 flu season may be similar to the 2003/2004 flu season, which also started early and was dominated by an emerging H3N2 sub-clade, A/Fujian/411/2002, which caused a large number of deaths, which included children.  The high number of adolescent deaths led to new regulations in the United States which made lab confirmed adolescent flu deaths reportable.  In 2003/2004 the H3N2 vaccine target, A/Panama/2007/1999, was poorly matched and was changed to a Fujian-like target, A/Wyoming/3/2003 (A/reassortant/NYMC X-147) in the following season.
For the 2012/2013 season the H3N2 target, A/Perth/16/2009, was changed to A/Victoria/361/2011, and the appearance of that sub-clade in the 2012/2013 season was widely touted as a match.  However, the week 48 FluView cited two H3N2 low reactors, and the CDC release of the first 50 H3N2 sequences from the new season identified the two low reactors as A/Hawaii/29/2012 and A/Iowa/14/2012 which were from collections made shortly after the start of the new season (on October 15 and 18, respectively).  However, at the time the CDC reported that these two isolates represented on 0.9% of the characterized samples and as of the week 51 report, that frequency had dropped to 0.7%, indicating the H3N2 low reactors were rare.  However, the sequences of the initial 50 cases indicated that closely related or identical sequences were present in a large number of 2012 isolates which were cited as matches.  The Iowa isolate had a limited number of changes, and the most glaring change was T128A, which abolished the glycosylation site at position 126.  This same change was seen in the Fujian-like vaccine target, A/Wyoming/3/2003.  This change was also in a closely related Iowa sequence, A/Iowa/15/2012 (which was said to be A/VICTORIA/361/2011-LIKE), as well as other 2012 isolates in the US (also called A/VICTORIA/361/2011-LIKE by the CDC) and the two H3N2 isolates from England this season.

However, the low reactor from Hawaii, A/Hawaii/29/2012, drew considerable attention from the CDC, and a closely related sequence, A/Hawaii/22/2012, have L157S, which is in a region (positions 157-160) that frequently produced low reactors.  This change has also been seen in three additional isolates from Hawaii.  Although all five of the sequences from Hawaii are virtually identical and all have L157S, the antigen characterization data highlights the internal inconsistencies in the testing.

Hawaii/22 was isolated from a July 09 collection from a 70M patient.  The CDC generated egg (accession number EPI397362) and mammalian (accession number EPI397072) isolates and both were characterized as A/PERTH/16/2009-LIKE.  This sequence has now been placed on an PR-8 genetic background (designated as A/Hawaii/22/2012 X-225 and A/Hawaii/22/2012 X-225A) for testing as an H3N2 vaccine target.  A sample from a second case (78M) in Hawaii, collected (September 3) prior to the start of the 2012/2013 season was also used to generate egg (ac cession number EPI398019) and mammalian (accession number EPI398033) isolates, both of which were characterized as A/VICTORIA/361/2011-LIKE.  This designation was also true for mammalian isolates from an October 1 case (13M), A/Hawaii/28/2012 and October 17 (F) case, A/Hawaii/30/2012.  However, the mammalian isolate from a September 15 case (96F), A/Hawaii/29/2012, was designated as a low reactor (A/VICTORIA/361/2011-LIKE (H3N2) LOW).
Thus, the CDC is testing an new H3N2 target, A/Hawaii/22/2012 X-225A, which has L157S, and is virtually identical to the recent low reactor from Hawaii, signaling the CDC’s awareness of the link between L157S and limited vaccine efficacy, as well as knowledge that multiple additional isolates from Hawaii are virtually identical, which is also true for recent isolates from the northeast, but these additional isolates are reported by the CDC as matches with the current vaccine target, A/Victoria/361/2011.

The antigen characterization data on the series of H3N2 isolates from Hawaii clearly demonstrate the limitations of the assay, as well as its use to create the illusion that the H3N2 circulating this season is a match with the current vaccine.

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