Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model.

Wen-Chun Liu,Florian Krammer,Francesco Berlanda-Scorza,Shirin Strohmeier,Bruce L Innis,Adolfo García-Sastre,Raffael Nachbagauer,Randy A Albrecht,Peter Palese,Daniel Stadlbauer,Alicia Solórzano

doi:10.3390/vaccines9010040

Abstract

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

Highlights

Chimeric HA-Based Influenza Vaccination Regimens Induce Durable Stalk-Reactive Immunity in Ferrets. The objective of this preclinical study was to assess the duration of protective immunity induced by the sequential immunization of ferrets with group 1 chimeric hemagglutinins [36,42,43]
To mimic pre-existing HA stalk immunity observed in humans, ferrets were primed by immunization with an influenza B virus expressing cH9/1 (B-cH9/1)
We previously reported on the efficacy of our sequential immunization regimen based on chimeric hemagglutinin (cHA)-based live-attenuated influenza virus vaccines (LAIV) vaccines to provide immunity against infection with human and avian influenza A viruses [31,32,33,34], which addresses two of the three universal influenza vaccines (UIV) criteria established by the National Institute of Allergy and Infectious Diseases (NIAID)

Summary

Introduction

The Advisory Committee on Immunization Practices (ACIP) recommends seasonal influenza virus vaccination for everyone 6 months of age or older [1]. Despite the availability of seasonal influenza virus vaccines, types A and B influenza viruses continue to co-circulate globally in humans [2]. Global seasonal influenza-associated respiratory deaths are estimated to range from 291,000 to 646,000 on an annual basis [4]. Current licensed seasonal influenza virus vaccines are formulated as inactivated influenza virus vaccines (IIV), live-attenuated influenza virus vaccines (LAIV), or recombinant hemagglutinin (HA) proteins [5]. Seasonal influenza vaccines provide immunity against infection by influenza viruses that antigenically match the vaccine strains [6,7,8,9,10,11,12,13]. The effectiveness of seasonal influenza vaccines to prevent laboratory-confirmed influenza varies by influenza season (with estimates ranging from 10 to 60%), with an estimate of 29%

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Discussion

Conclusion