Interleukin 12-containing influenza virus-like-particle vaccine elevate its protective activity against heterotypic influenza virus infection

Kenichi Maegawa,Shigeo Sugita,Youta Arasaki,Reiko Nerome,Kuniaki Nerome

doi:10.1016/j.heliyon.2020.e04543

Kenichi Maegawa, Shigeo Sugita + Show 3 more

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https://doi.org/10.1016/j.heliyon.2020.e04543

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Journal: Heliyon	Publication Date: Aug 1, 2020
Citations: 6	License type: cc-by

Affiliation: Japan Racing Association

Abstract

To produce monovalent and bivalent influenza vaccines composed of virus-like particles (VLPs) containing hemagglutinin (HA), we generated four recombinant Baculoviruses derived from Bombyx mori nuclear polyhedrosis virus (BmNPV) and Autographa california nuclear polyhedrosis virus (AcNPV). Monovalent Fukushima (A/tufted duck/Fukushima/16/2011 [H5N1]) (FkH5) and Anhui (A/Anhui/1/2013 [H7N9]) (AnH7) VLP influenza vaccines were produced in silkworm pupae infected with FkH5-BmNPV or AnH7-BmNPV. To produce a bivalent FkH5 and AnH7 vaccine, the pupae were simultaneously inoculated with FkH5-BmNPV and AnH7-BmNPV. Then, interleukin (IL)-containing bivalent vaccines were produced by Eri silkworm pupae following triple infection with FkH5-AcNPV, AnH7-AcNPV, and IL-12-AcNPV. Fluorescent antibody tests in Sf9 cells triple-infected with FkH5-AcNPV, AnH7-AcNPV, and IL-12-AcNPV showed coexpression of FkH5, AnH7, and IL-12 antigens, suggesting the presence of VLPs containing all three antigens. We then performed competitive hemagglutination inhibition (CHI) tests to calculate the VLP vaccine constituents. Inoculation with two recombinant viruses led to the production of bivalent vaccines containing very similar amounts of the H5 and H7 antigens, suggesting that our dual infection system can be used to produce bivalent VLP vaccines. Immunisation of mice with our developed monovalent and bivalent VLP vaccines induced the production of HI antibody, which protected against a sublethal dose of influenza virus. These IL-12-containing vaccines tended to display increased protection against hetero-subtype influenza viruses.

Highlights

Recent outbreaks of highly pathogenic avian influenza viruses have threatened both the poultry industry and human health [1, 2, 3]
Almost all the Sf9 cells infected with FkH5-Autographa california nuclear polyhedrosis virus (AcNPV), AnH7-AcNPV, or IL-12-AcNPV were positively stained with anti-H5HA serum, anti-H7HA serum, or anti-IL-12 antibody, respectively
Vaccines produced using this method may reduce the threat of highly pathogenic avian influenza virus infection in birds and humans

Summary

Introduction

Recent outbreaks of highly pathogenic avian influenza viruses have threatened both the poultry industry and human health [1, 2, 3]. The characteristics of the isolated viral genomes indicated that all human infections occurred at chicken markets in Hong Kong where diseased chickens were introduced from epizootic poultry farms [3, 5]. Avian influenza has attracted considerable public attention, and avian influenza vaccines have been developed using various technologies. These vaccines have been produced by various methods including: 1) using temperature-sensitive mutants [6], 2) cell culture [7], 3) hemagglutinin (HA)-containing virus-like particles (VLPs) [8, 9], and 4) DNA-based vaccines [10, 11]. With an aim to provide inexpensive, effective vaccines against avian influenza, we developed a recombinant baculovirus system for the large-scale production of H5 and H7

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