Selection of antigenically advanced variants of seasonal influenza viruses.

Chengjun Liu ,David E Wentworth,David F Burke,Jacqueline M Katz,Takato Odagiri,Masaki Imai,Eileen A Maher,Colin A Russell,Masato Hatta,Anne Kelso,Mutsumi Ito,Nancy J Cox,Ying Zhang,Masato Tashiro,Eugene Skepner,Gabriele Neumann,Makoto Ozawa,Peter R Wilker,Subash C Das,Sarah L James,Shinji Watanabe,Yuelong Shu,Yoshihiro Kawaoka,Tokiko Watanabe,Jihui Ping,Andrew S Taft,Derek J Smith,Kiyoko Iwatsuki‐Horimoto ,John W Mccauley ,Alexander Klimov ,Anthony Hanson ,Xinhua Xu ,Jianzhong Song ,Dayang Wang

doi:10.1038/nmicrobiol.2016.58

Abstract

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014–2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.Supplementary informationThe online version of this article (doi:10.1038/nmicrobiol.2016.58) contains supplementary material, which is available to authorized users.

Highlights

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses
haemagglutination inhibition (HI) assays were performed for 20 reference strains and for 32 and 56 mutant viruses isolated from the CUHK5250 and Kwangju/219 screens, respectively
With the current vaccine selection process, uncertainty remains as to whether the recommended vaccine virus will provide protective immunity against the epidemic strain

Summary

Introduction

Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014–2015 This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature. Antigenic cartography (an established method to visualize and analyse HI data8) is used to identify novel antigenic clusters that may necessitate the update of an influenza vaccine This experimental approach could identify novel antigenic clusters before they emerge in nature and complement the current vaccine selection process. These data demonstrate the importance of antigenic site Sa for A(H1N1) pdm[09] antigenicity

Methods

Findings

Conclusion