Anti-Influenza Protective Efficacy of a H6 Virus-Like Particle in Chickens.

Wan-Zhen Zhu,Ting-Chih Chen,Hui-Wen Chen,Shu-Yi Lin,Yi-Chi Wen

doi:10.3390/vaccines8030465

Abstract

H6 avian influenza viruses (AIVs) have a worldwide distribution, and they pose a potential concern for public health. In Taiwan, H6 AIVs have circulated in domestic chickens for more than 40 years, and certain strains have crossed the species barrier to infect mammals. With the goal of containing the disease, there is a pressing need to develop a safe and effective vaccine for pandemic preparedness. In this study, we prepared a virus-like particle (VLP) that consisted of the hemagglutinin (HA) and matrix protein 1 (M1) derived from a H6 AIV as a vaccine antigen, and we examined the immunogenicity and protective efficacy when combined with an adjuvant in a chicken model. Full-length HA and M1 protein genes were cloned and expressed using a baculovirus expression system, and VLPs were purified from the supernatant of insect cell cultures. We performed nanoparticle-tracking analysis and transmission electron microscopy to validate that the particle structure and properties resembled the native virions. In animal experiments, specific-pathogen-free chickens that received the H6 VLPs in combination with an adjuvant showed superior H6N1 virus-specific serum IgG and hemagglutination-inhibition antibody responses, which lasted more than 112 days. Following the H6N1 viral challenge, the vaccinated chickens showed reduced viral replication in the lungs, kidneys and conjunctival/cloacal shedding. The antibodies induced in the chickens by the vaccine were able to cross-react with the H6N1 human isolate and drifted avian H6N1 isolates. In summary, the H6 VLP vaccine elicited superb immunogenicity in vivo, and the use of an adjuvant further enhanced the antiviral protective efficacy. This vaccine formulation could potentially be used to manage H6 influenza virus infections in chickens.

Highlights

The influenza virus belongs to the family Orthomyxoviridae and has negative-sense single-stranded RNA genomes [1]
Based on two proteins on the surface of the virus, hemagglutinin (HA) and neuraminidase (NA), influenza A viruses can be divided into different subtypes
H6N1 antibodies have been detected from the poultry farmer of Taiwan [11]. These findings indicate that H6 avian influenza viruses (AIVs) can cross species barriers and pose a potential threat to human health

Summary

Introduction

The influenza virus belongs to the family Orthomyxoviridae and has negative-sense single-stranded RNA genomes [1]. Among the four types of influenza virus, the influenza A virus has the broadest host range. Based on two proteins on the surface of the virus, hemagglutinin (HA) and neuraminidase (NA), influenza A viruses can be divided into different subtypes. HA subtypes and 11 different NA subtypes have been documented [2]. H6 avian influenza viruses (AIVs) are the most commonly detected influenza viruses in wild birds and domestic poultry, and they have a broader host range than any other subtypes. An eight-year surveillance study from 1998 to 2006 indicated that H6 was the most prevalent subtype in wild birds from Europe and the Americas [3]

Objectives

Methods

Conclusion