Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus

Brianna L Bullard,Jennifer Debeauchamp,Eric A Weaver,Adam Rubrum,Richard J Webby,Bette Korber,Brigette N Corder

doi:10.1038/s41467-021-21508-6

Abstract

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Here, we utilize epigraph, a computational algorithm, to design a universal swine H3 influenza vaccine. The epigraph hemagglutinin proteins are delivered using an Adenovirus type 5 vector and are compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination leads to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduces weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination shows superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.

Highlights

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential
The resulting trivalent set of epigraph sequences provides the optimal coverage of potential linear epitopes in the population for a 3-protein set, minimizes the inclusion of rare epitopes that might result in type-specific immune responses, and artificial, each epigraph resembles natural HA proteins to enable both the induction of antibody and T-cell responses
We evaluated the Epigraph vaccine designer algorithm for the immunogen design of broadly cross-reactive swine H3 (swH3) HA to create a universal swH3 vaccine

Summary

Introduction

Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. Pigs are susceptible to swine, avian, and human influenza viruses, making them the perfect “mixing vessel” for novel reassorted influenza viruses[2,5] These novel reassorted viruses have significant pandemic potential if zoonosis occurs, as seen with 2009 H1N1 “swine flu” pandemic. This highlyreassorted swine-origin influenza virus quickly circulated the globe and infected a staggering 24% of the world’s human population[6,7]. IAV-S infection can cause tremendous economic loss to swine producers, with cost estimates as high as $10.31 per market pig[9]

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