Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

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.

Full Issue

“…Therefore, vaccination approaches focusing on the induction of humoral immunity have limitations. Stimulation of T-cell immunity may then provide better cross-protection, as more conserved antigens are involved in the activation of CMI (141,142) compared to B-cell epitopes, which may change due to immune evasion and therefore reduce vaccine efficacy if not regularly adjusted over time (143).…”

“…However, a promising possibility was demonstrated in Salmonella Seftenburg in which a Dlon DcpxR mutant strain displayed increased invasiveness in colonizing internal organs, but for a short duration (139). This lack of success in enhancing the immunogenicity of these noninvasive strains is particularly unfortunate regarding serogroup C Salmonella since these strains including Salmonella Infantis (140) and Salmonella Kentucky (141,142) have become predominant colonizers of poultry flocks in recent years, and Salmonella Infantis, at least, is frequently being transmitted through the food chain causing illness in humans (143,144).…”

“…Attenuated Histomonas will lose the capability to revert to virulence in vivo after fewer than 295 passages or about 15 wk in vitro (138,140). Various experiments in recent years have shown the efficacy and safety of attenuated Histomonas vaccines in chickens as well as in turkeys (141,142,143,144).…”

The Immunological Basis for Vaccination

“…Therefore, vaccination approaches focusing on the induction of humoral immunity have limitations. Stimulation of T-cell immunity may then provide better cross-protection, as more conserved antigens are involved in the activation of CMI (141,142) compared to B-cell epitopes, which may change due to immune evasion and therefore reduce vaccine efficacy if not regularly adjusted over time (143).…”

A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage

“…Virus-like particles (VLP) show high plasticity and scalability to develop multiple subtypes of influenza vaccines, including H5 [ 8 ], H6 [ 9 ], H7 [ 10 ], and H9 [ 11 ] subtypes, which are produced in various expression systems, such as insect cell-baculovirus [ 10 ], plant cells [ 12 ], and mammalian cells [ 13 ]. Furthermore, the innocuous VLP retains the structural and immunological properties of a native virus.…”