Design and characterization of a consensus hemagglutinin vaccine immunogen against H3 influenza A viruses of swine

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Vet Microbiol. 2019 Dec;239:108451. doi: 10.1016/j.vetmic.2019.108451. Epub 2019 Oct 12. Design and characterization of a consensus hemagglutinin vaccine immunogen against H3 influenza A viruses of swine.

Sun H¹, Sur JH², Sillman S³, Steffen D³, Vu HLX⁴.
Author information

1 Nebraska Center for Virology and Department of Animal Science, University of Nebraska, Lincoln, Nebraska, USA. 2 Department of Veterinary Pathology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. 3 School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, USA. 4 Nebraska Center for Virology and Department of Animal Science, University of Nebraska, Lincoln, Nebraska, USA. Electronic address: hiepvu@unl.edu.

Abstract

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene and a HA gene of a naturally occurring H3N2 IAV-S strain (designated H3-TX98) were expressed using the baculovirus expression system and emulsified in an oil-in-water adjuvant to be used for vaccination. Pigs vaccinated with H3-CON.1 immunogen elicited broader levels of cross-reactive neutralizing antibodies and interferon gamma secreting cells than those vaccinated with H3-TX98 immunogen. After challenge infection with a fully infectious H3N2 IAV-S isolate, the H3-CON.1-vaccinated pigs shed significantly lower levels of virus in their nasal secretions than the H3-TX98-vaccinated pigs. Collectively, our data provide a proof-of-evidence that the consensus immunogen approach may be effectively employed to develop a broadly protective vaccine against IAV-S.
Copyright ? 2019 The Authors. Published by Elsevier B.V. All rights reserved.


KEYWORDS:

Baculovirus expression; Hemagglutinin gene; Heterologous protection; Influenza A viruses of swine

PMID: 31767095 DOI: 10.1016/j.vetmic.2019.108451