PT  - JOURNAL ARTICLE
AU  - Sarah Cobey
AU  - Kaela Parkhouse
AU  - Benjamin S. Chambers
AU  - Hildegund C. Ertl
AU  - Kenneth E. Schmader
AU  - Rebecca A. Halpin
AU  - Xudong Lin
AU  - Timothy B. Stockwell
AU  - Suman R. Das
AU  - Emily Landon
AU  - Vera Tesic
AU  - Ilan Youngster
AU  - Benjamin Pinsky
AU  - David E. Wentworth
AU  - Scott E. Hensley
AU  - Yonatan H. Grad
TI  - Despite egg-adaptive mutations, the 2012-13 H3N2 influenza vaccine induced comparable antibody titers to the intended strain
AID  - 10.1101/158550
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 158550
4099  - http://biorxiv.org/content/early/2017/07/05/158550.short
4100  - http://biorxiv.org/content/early/2017/07/05/158550.full
AB  - Background Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A/H3N2. Failure to achieve consistently high VE has been attributed both to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in 2012-13 was attributed to egg-adaptive mutations that created antigenic mismatch between the intended (A/Victoria/361/2011) and actual vaccine strain (IVR-165).Methods We investigate the basis of the low VE in 2012-2013 by evaluating whether vaccinated and unvaccinated individuals were infected by different viral strains and assessing the serologic responses to A/Victoria/361/2011 and the IVR-165 vaccine strain in an adult cohort before and after vaccination.Results We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 as much as to IVR-165. These results are consistent with the hypothesis that vaccination served merely to boost preexisting cross-reactive immune responses, which provided limited protection against infection with the circulating influenza strains.Conclusions In contrast to suggestive analyses based on ferret antisera, low H3N2 VE in 2012-13 does not appear to be due to the failure of the egg-adapted strain to induce a response to the intended vaccine strain. Instead, low VE might have been caused by the emergence of anti-genically novel influenza strains and low vaccine immunogenicity in a subset of the population.