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

Authors

Brianna L. Bullard, University of Nebraska-Lincoln
Brigette N. Corder, University of Nebraska-Lincoln
Jennifer DeBeauchamp, St. Jude Children’s Research Hospital
Adam Rubrum, St. Jude Children’s Research Hospital
Bette Korber, Los Alamos National Laboratory
Richard J. Webby, St. Jude Children’s Research Hospital
Eric A. Weaver, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2-22-2021

Citation

NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-021-21508-6

Comments

Open access.

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.