Immunization with Plant-Derived Multimeric H5 Hemagglutinins Protect Chicken against Highly Pathogenic Avian Influenza Virus H5N1.

Hoang Trong Phan,Trang Huyen Vu,Van Thi Pham,Ha Hoang Chu,Thuong Thi Ho,Ngoc Bich Pham,Ulrike Gresch,Udo Conrad,Elsayed M Abdelwhab,Thomas C Mettenleiter,Armin Meister,Tran Xuan Hanh,David Scheibner

doi:10.3390/vaccines8040593

Abstract

Since 2003, H5N1 highly pathogenic avian influenza viruses (HPAIV) have not only caused outbreaks in poultry but were also transmitted to humans with high mortality rates. Vaccination is an efficient and economical means of increasing immunity against infections to decrease the shedding of infectious agents in immunized animals and to reduce the probability of further infections. Subunit vaccines from plants are the focus of modern vaccine developments. In this study, plant-made hemagglutinin (H5) trimers were purified from transiently transformed N. benthamiana plants. All chickens immunized with purified H5 trimers were fully protected against the severe HPAIV H5N1 challenge. We further developed a proof-of-principle approach by using disulfide bonds, homoantiparallel peptides or homodimer proteins to combine H5 trimers leading to production of H5 oligomers. Mice vaccinated with crude leaf extracts containing H5 oligomers induced neutralizing antibodies better than those induced by crude leaf extracts containing trimers. As a major result, eleven out of twelve chickens (92%) immunized with adjuvanted H5 oligomer crude extracts were protected from lethal disease while nine out of twelve chickens (75%) vaccinated with adjuvanted H5 trimer crude extracts survived. The solid protective immune response achieved by immunization with crude extracts and the stability of the oligomers form the basis for the development of inexpensive protective veterinary vaccines.

Highlights

The vaccination of humans and animals to protect against infectious diseases is an efficient preventive measure [1]
The solid protective immune response achieved by immunization with crude extracts and the stability of the oligomers form the basis for the development of inexpensive protective veterinary vaccines, especially suitable for application in developing countries and suiting demands for highly effective vaccines, simple and severe production strategies and efficient and applicable ways and methods for distribution and use
Our results clearly show the potential of H5 oligomers in plant crude extracts for the development of cheap protective veterinary vaccines meeting the demands of highly effective vaccines, simple and severe production strategies and efficient and applicable methods for distribution and use

Summary

Introduction

The vaccination of humans and animals to protect against infectious diseases is an efficient preventive measure [1]. Zoonotic pathogens that can infect animals as well as humans, such as avian flu [3] caused by orthomyxoviruses, are common sources of emerging infectious diseases. Avian flu caused strong damage to the poultry and the tourist industry in south-east Asia [4]. Pathogenic avian flu viruses were responsible for outbreaks in South Korea, China, Japan, USA, Canada and many European countries [5]. Influenza viruses constantly change via recombination to express different combinations of the major viral antigens hemagglutinin and neuraminidase and via mutagenesis [6,7] to escape the immune response of the host [8]

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Discussion

Conclusion