H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

Hang Xie,Yifei Xu,Anding Zhang,Olga Zoueva,Xing Li,Xianghong Jing,Courtney Finch,Yanhong Zhu,Ewan P Plant,Zhengshi Lin,Meng-Jung Chiang,Toshiaki Kawano,Yangqing Zhao,Xiu-Feng Wan,Nan Zhao,Zhiping Ye

doi:10.1038/srep15279

Hang Xie, Yifei Xu + Show 14 more

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https://doi.org/10.1038/srep15279

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The poor performance of 2014–15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009–10, 2010–11 and 2014–15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014–15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014–15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

Highlights

Low effectiveness of 2014–15 NH influenza vaccines has been attributed to mismatch of the H3 component with the circulating influenza A (H3) viruses
Seasonal influenza vaccine effectiveness essentially depends upon how well vaccine strains represent viruses circulating in the community
Study subjects who received 2014–15 NH vaccines had substantially lower levels of hemagglutination inhibition (HAI) antibodies cross-reacting with recent H3 variants than with TX/12e, indicating vaccination-induced antibodies could not efficiently neutralize emergent H3 viruses

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Introduction

Low effectiveness of 2014–15 NH influenza vaccines has been attributed to mismatch of the H3 component with the circulating influenza A (H3) viruses. Vaccine strain updates require a complex evaluation process, in which the main determinant is antigenic characterization of circulating viruses by standard ferret antisera; lesser determinants are genetic variations, prevalence rates, and geographic distributions of virus variants[4,5]. In this process, standard ferret post-infection antisera are obtained by inoculating seronegative ferrets with reference viruses representing recent and emergent influenza isolates. It has been suggested that ferret may not be an appropriate model to predict antigenic changes for influenza vaccine strain selection[8,9] It is yet unclear how different ferret system is from humans and why the differences occasionally lead to a mismatch vaccine strain, etc. We discussed the potential factors accounting for the differences observed above

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