Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice

Authors

Brigette N. Corder, University of Nebraska - LincolnFollow
Brianna L. Bullard, University of Nebraska - LincolnFollow
Jennifer L. DeBeauchamp, St. Jude Children's Research HospitalFollow
Natalia A. Ilyushina, U.S. Food and Drug AdministrationFollow
Richard J. Webby, St. Jude Children's Research HospitalFollow
Eric A. Weaver, University of Nebraska-LincolnFollow

ORCID IDs

Brianna L. Bullard

Eric A. Weaver

Date of this Version

2019

Citation

Vaccines 2019, 7, 195

Comments

© 2019 by the authors. Open access

doi:10.3390/vaccines7040195

Abstract

Annually, influenza A virus (IAV) infects ~5–10% of adults and 20–30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of IAV are needed. Here we developed and tested a novel mosaic H1 HA immunogen. The mosaic immunogen was optimized in silico to include the most potential B and T cell epitopes (PBTE) across a diverse population of human H1 IAV. Phylogenetic analysis showed that the mosaic HA localizes towards the non-pandemic 2009 strains which encompasses the broadest diversity in the H1 IAV population. We compared the mosaic H1 immunogen to wild-type HA immunogens and the commercial inactivated influenza vaccine, Fluzone. When analyzed by ELISA, the mosaic immunogen induced stronger antibody responses against all four diverse H1 HA proteins. When analyzing T cell responses, again the mosaic immunogen induced stronger cellular immunity against all 4 diverse HA strains. Not only was the magnitude of T cell responses strongest in mosaic immunized mice, the number of epitopes recognized was also greater. The mosaic vaccinated mice showed strong cross-protection against challenges with three divergent IAV strains. These data show that the mosaic immunogen induces strong cross-protective immunity and should be investigated further as a universal influenza vaccine.