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Commentary

H3N2 Low Reactor Abolishes HA Glycosylation Site
Recombinomics Commentary 15:00
December 31, 2012

•    153 (98.7%) of the 155 H3N2 influenza viruses tested have been characterized as A/Victoria/361/2011-like, the influenza A (H3N2) component of the 2012-2013 Northern Hemisphere influenza vaccine.
•    2 (1.3%) of the 155 H3N2 viruses tested showed reduced titers with antiserum produced against A/Victoria/361/2011.

•    279 (99.3%) of the 281 H3N2 influenza viruses tested have been characterized as A/Victoria/361/2011-like, the influenza A (H3N2) component of the 2012-2013 Northern Hemisphere influenza vaccine.

•    2 (0.7%) of the 281 H3N2 viruses tested showed reduced titers with antiserum produced against A/Victoria/361/2011.

The above FluView comments (in red) report the first two H3N2 low reactors in the 2012/2013 (in week 48), while the subsequent comments (in blue) from the current FluView (week 51) indicate these two low reactors represent 0.7% of the H3N2 isolates tested to date.  Although these numbers suggest the current H3N2 vaccine target is a good match the the virus circulating in the United States, the recently released CDC sequences from the first 50 cases in the 2012/2013 season indicated the low reactors cited above are common.


Thirty-five of the 50 sequences (from collections were between October 1 and November 14) are the same sub-clade as the H3N2 target, A/Victoria/361/2011 (which was also true for 12 of the 14 November collections).  The two sequences from the low reactors cited above were from Iowa and Hawaii and mapped with the Victoria/361 sub-clade.  However, each mapped on a separate branch and the reduced titers with the vaccine were due to two separate changes.


The Iowa sequence, A/Iowa/14/2012, had a limited number of HA changes, which included T128A which abolished the glycosylation site.  Glycosylation can create or hide important antigenic sites, and presence of T128A is a concern because the same change appeared in the A/Fujian/411/2002 vaccine target, A/Wyoming/3/2003 (A/reassortant/NYMC X-147).  The 2003/2004 H3N2 outbreak produced a dramatic spike the Pneumonia and Influenza (P&I) death rate, which included a large number of children.  The high number of adolescent deaths was followed by regulations which made adolescent infle3unza deaths reportable.  In week 51, the CDC reported a large spike in adolescent deaths, which is an undercount of the number of confirmed cases reported by state labs.


The number of 2012/2013 isolates with T128A (and the other HA associated found in Iowa/14) are listed below.


US 2012/2013 Isolates With T128A
A/Utah/27/2012                 November 12

A/Iowa/15/2012                 November 12
A/Rhode Island/08/2012   November 6
A/Alabama/18/2012          October 29
A/Pennsylvania/20/2012   October 24
A/New York/37/2012         October 21
A/New York/39/2012         October 20
A/Iowa/14/2012                 October 18
A/Texas/82/2012               October 11
A/Idaho/23/2012                October 9

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