Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus

Abstract

Swine influenza virus (SIV) is a significant burden on the pork industry and threat to human health due to its zoonotic potential. Here, we utilized epigraph, a computational algorithm, to design a universal swine H3 (swH3) influenza vaccine. The epigraph hemagglutinin proteins were delivered using an Adenovirus type 5 vector and compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination led to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduced 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, showed stronger levels of crossreactive antibodies and T-cell responses after immunization with epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination showed superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.

Strategies Targeting Hemagglutinin as a Universal Influenza Vaccine

“…A graphic visualization of the algorithm approach has been previously described [ 108 ]. The epigraph algorithm has been used to design a swine H3 immunogen, with the goal of reducing the pandemic potential of H3 from zoonotic transmission events [ 110 ]. This epigraph HA was expressed in a replication-defective Adenovirus vector and vaccination of mice induced increased cross-reactive antibodies as compared a wildtype HA or the commercial vaccine, with protective HI titers to fourteen of the twenty diverse swine H3 influenza virus strains.…”