Single dose of multi-clade virus-like particle vaccine protects chickens against clade 2.3.2.1 and clade 2.3.4.4 highly pathogenic avian influenza viruses

Yong-Myung Kang,Hyun-Kyu Cho,Seong Yup Kim,Su Jin Lee,Hyun-Mi Kang,Seo-Jeong Park,Myoung-Heon Lee,Min-Chul Kim,Jung-Won Park,Do-Young Kim,Ju Hun Kim

doi:10.1038/s41598-021-93060-8

Abstract

Virus-like particles (VLPs) are recognized as an alternative vaccine platform that provide effective protection against various highly pathogenic avian influenza viruses (HPAIVs). Here, we developed multi-clade VLPs expressing two HAs (a chimera of clade 2.3.2.1c and clade 2.3.4.4c HA) within a single vector. We then compared its protective efficacy with that of a monovalent VLP and evaluated its potency against each homologous strain. Chickens vaccinated with the multi-clade VLP shed less virus and were better protected against challenge than birds receiving monovalent vaccines. Single vaccination with a multi-clade VLP resulted in 100% survival, with no clinical symptoms and high levels of pre-challenge protective immunity (7.6–8.5 log2). Moreover, the multi-clade VLP showed high productivity (128–256 HAU) both in the laboratory and on a large scale, making it cheaper than whole inactivated vaccines produced in eggs. However, the PD50 (protective dose 50%) of the multi-clade VLP against clades 2.3.2.1c and 2.3.4.4c was < 50 PD50 (28 and 42 PD50, respectively), and effective antibody response was maintained for 2–3 months. This multi-clade VLP protects against both clades of HPAI viruses and can be produced in high amounts at low cost. Thus, the vaccine has potential as a pandemic preparedness vaccine.

Highlights

Pathogenic avian influenza (HPAI) has been circulating in wild birds and poultry worldwide since the first H5N1 avian influenza virus, A/Goose/Guangdong/1/96, was identified in China in 19961,2
We manufactured a multi-clade Virus-like particles (VLPs) vaccine by inserting the hemagglutination activity (HA) sequence of clade 2.3.2.1c(chimera) and 2.3.4.4c vaccine strains from the Korean AI national antigen bank
We compared the efficacy of monovalent and multi-clade VLP vaccines in specific pathogen free (SPF) chickens challenged with homologous strains

Summary

Introduction

Pathogenic avian influenza (HPAI) has been circulating in wild birds and poultry worldwide since the first H5N1 avian influenza virus, A/Goose/Guangdong/1/96, was identified in China in 19961,2. Novel HPAI H5Nx viruses, including various NA, have emerged continuously due to extensive genetic reassortment activity; various clades have emerged due to genetic evolution and antigenic drift[3,4,5]. Persistent HPAI outbreaks on poultry farms in many countries have been caused by mutated viruses, resulting in serious economic losses[1]. Since the emergence of H5N1 on a poultry farm in 2003, H5 HPAI outbreaks have occurred continuously, and new influenza viruses and genotypes have been introduced into K orea[7,8]. A vaccine based on VLP requires stronger product development through further studies examining multi-subunit, chimeric, and other types of VLPs; such studies should focus on delivery of sufficient amounts of VLP antigen because these vaccines will not be competitive in the market unless they are both productive and cost-effective[21]

Methods

Results

Conclusion