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First US 2013 H3N2 Sequence Has T128A
Recombinomics Commentary 14:15
February 2, 2013

The CDC has released its first set of 2013 H3N2 sequences (at GISAID), A/Virginia/03/2013, from a patient (76F) in Virginia, collected on January 4.  The H3 sequences had T128A, which abolishes the glycosylation site at position 126.  This change is becoming increasingly common in H3N2 sequences in the United States as well as across the world, including recent sequences in Europe and Africa.  This same change was present in the vaccine target for the 2004-05 season, A/Wyoming/03/2003, which was developed after the severed 2003-04 season which featured an H3N2 related to A/Fujian/411/2002.  This Fujian H3N2 produced a Pneumonia and Influenza Death Rate of 10% in the United States which was associated with 154 pediatric deaths.  The high fatality rate led to requirements for the reporting of all flu lab confirmed pediatric deaths in the United States, and some states also made the reporting of all adult fatal influenza cases under the age of 65 reportable also.

The Virginia sequence is closely related to A/Iowa/14/2012, which is one of the two H3N2 sequences this season that the CDC has designated as a low reactor, indicating the current H3N2 vaccine poorly recognizes this sequences, which is almost certainly largely due to the loss of the glycosylation site at position 126, which was also linked to the spread of H3N2 in 2003-04.  In addition to the 2013 Virginia sequence, the CDC also released 6 additional December 2012 sequences, and 4 of the 6 are closely related to the Virginia sequence and have T128A (A/New Hampshire/21/2012, A/Wisconsin/51/2012, and A/Kansas/16/2012). 

In addition to these four recently released December sequences, other US sequences with an H3 identical to the Virginia sequence include A/New York/47/2012, A/Oklahoma/3059/2012, and A/Pennsylvania/20/2012.  Moreover, other 2013 isolates have an identical H3 sequence includes those from Germany (A/Nordrhein-Westfalen/1/2013), France (A/Clermont-Ferrand/14/2013), and Denmark (A/Denmark/17/2013 and A/Denmark/25/2013).

In addition to the 2013 sequences which are identical to the Virginia H3 sequences, earlier 2012 H3 sequences are also identical.  These include sequences from France (A/Nord Pas de Calais/2000/2012, A/Poitiers/2407/2012, A/Annecy/2806/2012, and A/Paris/1966/2012), Senegal (A/Dakar/15/2012, A/Dakar/14/2012, A/Dakar/04/2012), Spain (A/Lisboa/SU15/2012), Denmark (A/Denmark/74/2012 and A/Denmark/113/2012,).

Moreover, a large series of sequences which have T128A and are closely related to the Virginia sequences are widespread including sequences that differ by a single nucleotide including sequences from the United States (A/Massachusetts/15/2012, A/Texas/82/2012, A/Iowa/15/2012), Denmark (A/Denmark/50/2013, A/Denmark/88/2012, A/Denmark/77/2012), Greece (A/Athens GR/14/2013), China (A/Hong Kong/8118/2012), Senegal (A/Dakar/16/2012), and France (A/Paris/1987/2012).

Other closely related sequences with T128A include all 10 recent sequences from England as well as many more sequences from the United States and the countries listed above (see full list below).

This sub-clade is becoming increasing widespread and will further lower the effectiveness of the current vaccine, which was at 55% in the United States, based on early collections, when the frequency of T128A was lower, as well as the frequency of 45% in Canada, where H3N2 dominates.
Recent H3 sequences with T128A (including 2004-05 vaccine target, A/Wyoming/03/2003)
 EPI417315 A/VICTORIA/918/2012 

 EPI417309 A/VICTORIA/886/2012 
 EPI417291 A/SOUTH AUSTRALIA/167/2012 
 EPI417273 A/SOUTH AUCKLAND/120/2012 
 EPI417225 A/Virginia/03/2013 
 EPI417222 A/New Hampshire/21/2012 
 EPI417204 A/Wisconsin/51/2012 
 EPI417201 A/Kansas/16/2012 
 EPI417198 A/Massachusetts/15/2012 
 EPI417102 A/Galicia/13035/2012 
 EPI417082 A/Aragon/13027/2012 
 EPI417071 A/Haute_Normandie/2022/2012 
 EPI417067 A/Nord_Pas_de_Calais/2000/2012 
 EPI417064 A/Paris/1987/2012 
 EPI417061 A/Paris/1966/2012 
 EPI417029 A/Nord Pas de Calais/2000/2012 
 EPI417027 A/Lisboa/SU15/2012 
 EPI417025 A/Haute Normandie/2022/2012 
 EPI417023 A/Dakar/16/2012 
 EPI417021 A/Dakar/15/2012 
 EPI417019 A/Dakar/14/2012 
 EPI417017 A/Dakar/08/2012 
 EPI417015 A/Dakar/04/2012 
 EPI417001 A/Athens GR/14/2013 
 EPI416522 A/Schleswig Holstein/7/2012 
 EPI416518 A/Poitiers/2745/2012 
 EPI416516 A/Poitiers/2407/2012 
 EPI416512 A/Nordrhein-Westfalen/1/2013 
 EPI416496 A/England/676/2012 
 EPI416494 A/England/670/2012 
 EPI416492 A/England/668/2012 
 EPI416490 A/England/625/2012 
 EPI416488 A/Clermont-Ferrand/14/2013 
 EPI416478 A/Annecy/2806/2012 
 EPI416262 A/Austria/11/2013 
 EPI416260 A/Austria/10/2013 
 EPI416258 A/Denmark/82/2012 
 EPI416257 A/Denmark/77/2012 
 EPI416256 A/Denmark/74/2012 
 EPI416254 A/Denmark/115/2012 
 EPI416253 A/Denmark/113/2012 
 EPI416251 A/Denmark/88/2012 
 EPI416246 A/Denmark/50/2013 
 EPI416245 A/Denmark/25/2013 
 EPI416244 A/Denmark/17/2013 
 EPI416243 A/Denmark/117/2012 
 EPI416242 A/Denmark/114/2012 
 EPI416241 A/Denmark/107/2012 
 EPI416184 A/Washington/61/2012 
 EPI416181 A/Washington/60/2012 
 EPI416155 A/North Carolina/28/2012 
 EPI416152 A/New York/47/2012 
 EPI416127 A/Iowa/22/2012 
 EPI416121 A/Idaho/38/2012 
 EPI416118 A/Idaho/37/2012 
 EPI413268 A/Laos/O095/2012 
 EPI413255 A/YAMAGUCHI/33/2012 
 EPI413207 A/YAMAGUCHI/30/2012 
 EPI408480 A/Austria/122/2012
 EPI408126 A/Niedersachsen/29/2012 
 EPI408117 A/England/593/2012 
 EPI408115 A/England/587/2012 
 EPI408113 A/England/586/2012 
 EPI408111 A/England/575/2012 
 EPI407622 A/Oklahoma/3059/2012 
 EPI407405 A/Idaho/24/2012 
 EPI407312 A/Alabama/24/2012 
 EPI407304 A/Nevada/27/2012 
 EPI407302 A/Montana/13/2012 
 EPI407299 A/Florida/46/2012 
 EPI407288 A/ENG/574/2012 
 EPI407285 A/ENG/570/2012 
 EPI407150 A/Taiwan/880/2012 
 EPI407149 A/Taiwan/879/2012 
 EPI407146 A/YAMAGUCHI/31/2012 
 EPI407145 A/SHIZUOKA/68/2012 
 EPI407090 A/Washington/53/2012 
 EPI407087 A/Minnesota/17/2012 
 EPI407006 A/HYOGO/3059/2012 
 EPI406999 A/YOKOHAMA/159/2012 
 EPI406995 A/YAMAGUCHI/30/2012 
 EPI406200 A/YAMANASHI/300/2012 
 EPI406199 A/YAMANASHI/297/2012 
 EPI406198 A/YOKOHAMA/155/2012 
 EPI406069 A/Utah/27/2012 
 EPI404997 A/Idaho/23/2012 
 EPI404971 A/Iowa/14/2012 
 EPI404965 A/New York/39/2012 
 EPI404947 A/Rhode Island/08/2012 
 EPI404944 A/Alabama/18/2012 
 EPI404938 A/Pennsylvania/20/2012 
 EPI404932 A/Texas/82/2012 
 EPI404927 A/New York/39/2012 
 EPI404911 A/Iowa/15/2012 
 EPI401735 A/New York/37/2012 
 EPI400061 A/Kenya/152/2011 
 EPI399657 A/Alabama/17/2012 
 EPI398030 A/Washington/50/2012 
 EPI397564 A/Alabama/17/2012 
 EPI394823 A/North Carolina/21/2012 
 EPI394256 A/PHILIPPINES/3/2012 
 EPI391234 A/Hong Kong/8118/2012 
 EPI390126 A/reassortant/NYMC X-147 
 EPI385944 A/Wyoming/3/2003 
 EPI382778 A/Hong Kong/8146/2012 
 EPI382725 A/Hong Kong/8118/2012 
 EPI353763 A/CastillaLaMancha/RR9008/2012
 EPI269372 A/NYMC X-147 (Puerto Rico/8/1934-Wyoming/03/2003)
 EPI241911 A/NYMC X-149C6(Puerto Rico/8/1934-Wyoming/03/2003)
 EPI160210 A/Wyoming/03/2003
 EPI152388 A/Wyoming/03/2003
 EPI146266 A/Wyoming/WY-2003100054/2003
 EPI116037 A/Wyoming/3e5/2003
 EPI116034 A/Wyoming/3e8/2003
 EPI116032 A/Wyoming/3e/2003
 EPI116030 A/Wyoming/3c/2003
 EPI20229 A/Wyoming/03/2003 

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