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Conserved antigen structures and antibody-driven variations on foot-and-mouth disease virus serotype A revealed by bovine neutralizing monoclonal antibodies.

Authors :
Li, Kun
He, Yong
Wang, Li
Li, Pinghua
Bao, Huifang
Huang, Shulun
Zhou, Shasha
Zhu, Guoqiang
Song, Yali
Li, Ying
Wang, Sheng
Zhang, Qianliang
Sun, Pu
Bai, Xingwen
Zhao, Zhixun
Lou, Zhiyong
Cao, Yimei
Lu, Zengjun
Liu, Zaixin
Source :
PLoS Pathogens; 11/20/2023, Vol. 19 Issue 11, p1-25, 25p
Publication Year :
2023

Abstract

Foot-and-mouth disease virus (FMDV) serotype A is antigenically most variable within serotypes. The structures of conserved and variable antigenic sites were not well resolved. Here, a historical A/AF72 strain from A22 lineage and a latest A/GDMM/2013 strain from G2 genotype of Sea97 lineage were respectively used as bait antigen to screen single B cell antibodies from bovine sequentially vaccinated with A/WH/CHA/09 (G1 genotype of Sea97 lineage), A/GDMM/2013 and A/AF72 antigens. Total of 39 strain-specific and 5 broad neutralizing antibodies (bnAbs) were isolated and characterized. Two conserved antigenic sites were revealed by the Cryo-EM structures of FMDV serotype A with two bnAbs W2 and W125. The contact sites with both VH and VL of W125 were closely around icosahedral threefold axis and covered the B-C, E-F, and H-I loops on VP2 and the B-B knob and H-I loop on VP3; while contact sites with only VH of W2 concentrated on B-B knob, B-C and E-F loops on VP3 scattering around the three-fold axis of viral particle. Additional highly conserved epitopes also involved key residues of <subscript>VP1</subscript>58, <subscript>VP1</subscript>147 and both <subscript>VP2</subscript>72 / <subscript>VP1</subscript>147 as determined respectively by bnAb W153, W145 and W151-resistant mutants. Furthermore, the epitopes recognized by 20 strain-specific neutralization antibodies involved the key residues located on VP3 68 for A/AF72 (11/20) and VP3 175 position for A/GDMM/2013 (9/19), respectively, which revealed antigenic variation between different strains of serotype A. Analysis of antibody-driven variations on capsid of two virus strains showed a relatively stable VP2 and more variable VP3 and VP1. This study provided important information on conserve and variable antigen structures to design broad-spectrum molecular vaccine against FMDV serotype A. Author summary: Bovine is susceptible host to foot-and-mouth disease virus (FMDV) and neutralization antibodies provide vital protection in defending viral infection, concurrently driving viral evolution in host. Herein, using single B cell antibody technology, we isolated and characterized a panel of 44 bovine-derived neutralizing monoclonal antibodies against FMDV serotype A, including 39 strain-specific and 5 broad neutralizing antibodies (bnAbs) against both A22 and Sea97 lineages representative strains. We revealed at least four conserved antigen sites including two sites on VP1 and each one on VP2/VP3, which exist on viral capsid surface and can induce bnAb response to FMDV serotype A in vivo. Additionally, antibody-driven variations showed shrinkage and appearance of strain-specific antigen epitopes were found on VP3 68 and 175 positions of FMDV serotype A. To sum up, this study provided conserved antigen structures and strain-specific epitopes information to guide the design of broad vaccine molecular against FMDV serotype A. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15537366
Volume :
19
Issue :
11
Database :
Complementary Index
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
173719831
Full Text :
https://doi.org/10.1371/journal.ppat.1011811