Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection



You, Lei, Chen, Junbo, Cheng, Yibing, Li, Yu, Chen, Yao-Qing, Ying, Tianlei, Turtle, Lance ORCID: 0000-0002-0778-1693 and Yu, Hongjie
(2023) Antibody signatures in hospitalized hand, foot and mouth disease patients with acute enterovirus A71 infection. PLOS PATHOGENS, 19 (6). e1011420-.

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Abstract

Enterovirus A71 (EV-A71) infection is a major cause of severe hand, foot and mouth disease (HFMD) in young children. The characteristics of EV-A71 neutralizing antibodies in HFMD patients are not well understood. In this study, we identified and cloned EV-A71-neutralizing antibodies by single cell RNA and B cell receptor sequencing of peripheral blood mononuclear cells. From 145 plasmablasts, we identified two IgG1 monoclonal antibodies (mAbs) and six IgM mAbs that neutralized EV-A71. Four of the IgM mAbs harbor germline variable sequences and neutralize EV-A71 potently. Two genetically similar IgM antibodies from two patients have recurrent heavy chain variable domain gene usage and similar complementarity-determining region 3 sequences. We mapped the residues of EV-A71 critical for neutralization through selection of virus variants resistant to antibody neutralization in the presence of neutralizing mAbs. The residues critical for neutralization are conserved among EV-A71 genotypes. Epitopes for the two genetically similar antibodies overlap with the SCARB2 binding site of EV-A71. We used escape variants to measure the epitope-specific antibody response in acute phase serum samples from EV-A71 infected HFMD patients. We found that these epitopes are immunogenic and contributed to the neutralizing antibody response against the virus. Our findings advance understanding of antibody response to EV-A71 infection in young children and have translational potential: the IgM mAbs could potentially be used for prevention or treatment of EV-A71 infections.

Item Type: Article
Uncontrolled Keywords: Leukocytes, Mononuclear, Humans, Enterovirus, Enterovirus A, Human, Enterovirus Infections, Hand, Foot and Mouth Disease, Immunoglobulin M, Antibodies, Monoclonal, Antibodies, Viral, Antigens, Viral, Epitopes, Child, Child, Preschool, Antibodies, Neutralizing
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 24 Jul 2023 14:54
Last Modified: 24 Jul 2023 14:54
DOI: 10.1371/journal.ppat.1011420
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3171842