Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness.

Hirotaka Hayashi,Keita Matsuno,Yoshihiro Sakoda,Masatoshi Okamatsu,Hiroshi Kida,Enkhbold Bazarragchaa,Norikazu Isoda,Naoki Nomura

doi:10.3390/vaccines8040768

Abstract

H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.

Highlights

Influenza A virus is an enveloped virus containing single-stranded, eight-segmented, negative-sense RNA; it is categorized into 18 hemagglutinin (HA) and 11 neuraminidase (NA)subtypes [1]
This study aimed to select a candidate vaccine strain from our virus library, prepare a vaccine, and evaluate the vaccine’s potency in a mouse model
Madin–Darby canine kidney (MDCK) cells were maintained in minimum essential medium (MEM; Nissui Pharmaceutical, Tokyo, Japan) supplemented with 10% non-immobilized fetal calf serum

Summary

Introduction

Influenza A virus is an enveloped virus containing single-stranded, eight-segmented, negative-sense RNA; it is categorized into 18 hemagglutinin (HA) and 11 neuraminidase (NA)subtypes [1]. Influenza A virus is an enveloped virus containing single-stranded, eight-segmented, negative-sense RNA; it is categorized into 18 hemagglutinin (HA) and 11 neuraminidase (NA). HA binds to the glycan of the host cells, but the glycan structure differs among animal species. It is thought that an influenza pandemic may originate from influenza viruses circulating among pigs. Pigs play the role of a “mixing vessel” by expressing both human- and avian-type receptors to influenza viruses in respiratory epithelial cells and cause a reassortment between two types of influenza viruses [2]. Waterfowl are natural hosts of influenza viruses, and viral antigenicity is conserved within the natural host [3]. As preparedness against an influenza pandemic, influenza viruses perpetuated in waterfowl, whose antigenicity is highly conserved, have been isolated

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