A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies

Raffael Nachbagauer,Francesco Berlanda-Scorza,Florian Krammer,Alicia Solórzano,Randy A Albrecht,Angela Choi,Teddy John Wohlbold,Peter Palese,Adolfo García-Sastre,Wen-Chun Liu,Madhusudan Rajendran,Talia Atlas

doi:10.1038/s41541-017-0026-4

Abstract

Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved—but immuno-subdominant—hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.

Highlights

Influenza virus infections cause significant morbidity and mortality worldwide every year.[1]
The objective of this study was the preclinical evaluation of a sequential immunization strategy with chimeric HAs (cHAs) to induce HA stalkspecific immune responses that confer protection against influenza virus infection
The cH8/1 live attenuated influenza virus vaccines (LAIVs) strain proved to be non-pathogenic in an intravenous pathogenicity test in chickens performed at the United States Department of Agriculture (USDA) according to the World Organization for Animal Health procedures for testing pathogenicity of influenza viruses

Summary

Introduction

Influenza virus infections cause significant morbidity and mortality worldwide every year.[1]. Seasonal influenza viruses, which cause annual epidemics, constantly escape from herd immunity by antigenic drift of their. Mismatches between vaccine strains and circulating strains cause a substantial decrease in vaccine efficacy.[3] In addition, the specter of a new influenza pandemic resulting from the unpredictable emergence of a new antigenically shifted virus from an animal reservoir represents an unsurmountable challenge for current influenza vaccines. Production and distribution of matched pandemic vaccines takes approximately 6 months—an interval during which the human population is insufficiently protected from a pandemic influenza virus outbreak.[4] The development of a pan-influenza vaccine that confers protection against homologous, drifted and shifted influenza virus strains would abolish the need for annual reformulation, and mitigate disease burden following the emergence of a pandemic influenza virus strain

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