Abstract
The continuous evolution of the H7N9 avian influenza virus suggests a potential outbreak of an H7N9 pandemic. Therefore, to prevent a potential epidemic of the H7N9 influenza virus, it is necessary to develop an effective crossprotective influenza vaccine. In this study, we developed H7N9 virus-like particles (VLPs) containing HA, NA, and M1 proteins derived from H7N9/16876 virus and a helper antigen HMN based on influenza conserved epitopes using a baculovirus expression vector system (BEVS). The results showed that the influenza VLP vaccine induced a strong HI antibody response and provided effective protection comparable with the effects of commercial inactivated H7N9 vaccines against homologous H7N9 virus challenge in chickens. Meanwhile, the H7N9 VLP vaccine induced robust crossreactive HI and neutralizing antibody titers against antigenically divergent H7N9 viruses isolated in wave 5 and conferred on chickens complete clinical protection against heterologous H7N9 virus challenge, significantly inhibiting virus shedding in chickens. Importantly, supplemented vaccination with HMN antigen can enhance Th1 immune responses; virus shedding was completely abolished in the vaccinated chickens. Our study also demonstrated that viral receptor-binding avidity should be taken into consideration in evaluating an H7N9 candidate vaccine. These studies suggested that supplementing influenza VLP vaccine with recombinant epitope antigen will be a promising strategy for the development of broad-spectrum influenza vaccines.
Highlights
In March 2013, a novel H7N9 subtype of avian influenza virus infection was discovered in human cases in China [1]
The H7N9 virus-like particles (VLPs) were produced in High Five insect cells, which were coinfected with recombinant baculovirus expressing HA, NA, and M1
The H7N9 VLPs in the study were produced using High Five cells coinfected with recombinant baculovirus (rBV) expressing HA, NA, and M1 at an multiplicity of infection (MOI) of 2:1:2
Summary
In March 2013, a novel H7N9 subtype of avian influenza virus infection was discovered in human cases in China [1]. The virus has spread rapidly throughout the country, leading to several waves of outbreaks. After the emergence of the highly pathogenic H7N9 avian influenza virus during the fifth wave, the H7N9 virus caused a sharp rise in human infection, resulting in 1,568. H7N9 Virus-Like Particles Subunit Vaccine laboratory-confirmed cases and 616 deaths as of July 7, 2021 (http://www.fao.org/ag/againfo/programmes/en/empres/H7N9/ situation_update.html). Some novel biological features of the H7N9 virus, such as immune escape mutations and antigenic drift were discovered in H7N9 variants [2–4]. The continuous evolution of the H7N9 virus poses a dual threat to public health and the poultry industry, and it is imperative to protect against H7N9 influenza infection
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