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

• Published in: Nature communications Vol. 12; no. 1; p. 1203
• Main Authors: Bullard, Brianna L., Corder, Brigette N., DeBeauchamp, Jennifer, Rubrum, Adam, Korber, Bette, Webby, Richard J., Weaver, Eric A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/44; 60 APPLIED LIFE SCIENCES; 631/250/2152; 631/250/254; 631/250/255; 631/250/590; 82/80; Adaptive immunity; Agricultural industry; Algorithms; Animal models; Animals; Antibodies; Antibody Formation - immunology; BASIC BIOLOGICAL SCIENCES; Computer applications; Cross Reactions - immunology; Divergence; Epitopes - immunology; Female; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Humanities and Social Sciences; Humans; Immunity; Immunization; Infectious diseases; Influenza; Influenza A; Influenza A virus - immunology; Influenza Vaccines - immunology; Influenza, Human - blood; Influenza, Human - immunology; Influenza, Human - virology; Lung - pathology; Lung - virology; Lymphocytes T; Male; Mice; Mice, Inbred BALB C; multidisciplinary; Orthomyxoviridae Infections - blood; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Public health; Science; Science (multidisciplinary); Swine; Swine H3 influenza; T-Lymphocytes - immunology; Vaccination; Vaccines; Viruses; Weight Loss; Weight reduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21508-6

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. A range of Influenza vaccines have been linked to induction of adaptive immunity in a number of animal models. Here, the authors utilize a computational design strategy and produce a swine H3 influenza vaccine which shows enhanced efficacy in both murine and porcine infectious disease models.