Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus
-
Published:2023-12-12
Issue:6
Volume:11
Page:
-
ISSN:2165-0497
-
Container-title:Microbiology Spectrum
-
language:en
-
Short-container-title:Microbiol Spectr
Author:
Wan Zhimin1234ORCID, Gong Jianxi1234, Sang Jianjun5, Jiang Wenjie1234, Zhao Zhehong1234, Tang Ting1234, Li Yafeng1234, Zhao Yichao5, Kan Qiuqi1234, Xie Quan1234, Li Tuofan1234, Shao Hongxia123, Gao Wei123, Qin Aijian123ORCID, Ye Jianqiang1234ORCID
Affiliation:
1. Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University , Yangzhou, Jiangsu, China 2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses , Yangzhou, Jiangsu, China 3. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University , Yangzhou, Jiangsu, China 4. Institute of Agricultural Science and Technology Development, Yangzhou University , Yangzhou, Jiangsu Province, China 5. Sinopharm Yangzhou VAC Biological Engineering Co. Ltd , Yangzhou, Jiangsu, China
Abstract
ABSTRACT
H6 influenza A viruses are enzootic and genetically diverse in both domestic poultry and wild birds, occasionally causing spillovers to mammals, including humans, posing threat to public health. However, the antigenic sites of the hemagglutinin (HA) of H6 are poorly understood. In this study, a panel of murine monoclonal antibodies (MAbs) with different reactivity spectra against HA of H6 was generated and nine key residues of antigenic epitopes in H6 were identified through escape mutants of these MAbs. Of these, residues 139 and 140 belonged to antigenic Sa, residue 89 belonged to antigenic Cb, residue 149 belonged to Ca2, while residue 221 belonged to Ca1 regarding the H1 antigenic sites. However, the other four residues 69, 120, 124, and 246 were not located in the identified antigenic regions of H1. Although most HA variants of the escape mutants had the preference for avian-like receptor, whereas escape mutants m3B9 and m4C2 increased the binding affinity for both avian and human-like receptors, and m1A5 and m6D11 decreased the binding affinity for avian-like receptors. Moreover, a single dose of MAbs 4C2 or 6E3 could fully protect mice against lethal challenge of mouse-adapted A/Eurasian teal/Jiangxi/2018WB0417(H6N2) (MA E-Teal/417) in the prophylactic treatment and also could provide partial protection in the therapeutic treatment. Overall, the generated MAbs and the identified key residues of antigenic epitopes not only provide novel insights into the key markers for monitoring the antigenic variation of H6 but also demonstrate the potential for developing MAb-based passitive treatments for H6.
IMPORTANCE
Since the escape immunity of influenza A viruses (IAVs) is mainly caused by the continuous antigenic variations in HA, the identification of key antigenic epitopes is crucial for better understanding of the escape immunity and vaccine development for IAVs. The antigenic sites of several HA subtypes, including H1, H3, H5, and H9, have been well characterized, whereas those of H6 subtype are poorly understood. Here, we mapped nine key residues of antigenic epitopes in H6 through escape mutants using a panel of MAbs. Moreover, MAbs 4C2 and 6E3, targeting 140 and 89 residues, respectively, could protect mice against lethal challenge of MA E-Teal/417. These key residues of antigenic epitopes identified here provide the molecular targets for further elucidating the antigenic evolution of H6 and better preparing the vaccine against H6 IAV.
Funder
JST | Jiangsu Natural Science Foundation | Basic Research Program of Jiangsu Province MOST | National Natural Science Foundation of China Priority Academic Program Development of Jiangsu Higher Education Institutions
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology
Reference35 articles.
1. Characterization and ecology of a type A influenzavirus isolated from a sheawater;Downie JC;Bull World Health Organ,1973 2. Spatial, Temporal, and Species Variation in Prevalence of Influenza A Viruses in Wild Migratory Birds 3. Surveillance of avian influenza viruses in South Korea between 2012 and 2014 4. Cardona C . 2004. “Low-pathogenicity avian influenza outbreaks in commercial poultry in California” The threat of pandemic influenza: are we ready? Workshop summary, Proceedings for the Symposium on pandemic influenza preparedness; Institute of Medicine 5. Avian Influenza in the Western Hemisphere Including the Pacific Islands and Australia
|
|