RT Journal Article SR Electronic T1 Despite egg-adaptive mutations, the 2012-13 H3N2 influenza vaccine induced comparable antibody titers to the intended strain JF bioRxiv FD Cold Spring Harbor Laboratory SP 158550 DO 10.1101/158550 A1 Sarah Cobey A1 Kaela Parkhouse A1 Benjamin S. Chambers A1 Hildegund C. Ertl A1 Kenneth E. Schmader A1 Rebecca A. Halpin A1 Xudong Lin A1 Timothy B. Stockwell A1 Suman R. Das A1 Emily Landon A1 Vera Tesic A1 Ilan Youngster A1 Benjamin Pinsky A1 David E. Wentworth A1 Scott E. Hensley A1 Yonatan H. Grad YR 2017 UL http://biorxiv.org/content/early/2017/07/05/158550.abstract 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.