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PLoS Pathog. 2019 Nov 7;15(11):e1008061. doi: 10.1371/journal.ppat.1008061. eCollection 2019 Nov.

Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins.

Author information

1
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
2
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America.
3
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
4
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
5
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
6
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
7
Integrated Biotherapeutics Inc., Rockville, Maryland, United States of America.
8
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
9
Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America.
10
Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America.

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.

PMID:
31697791
PMCID:
PMC6837291
DOI:
10.1371/journal.ppat.1008061
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Conflict of interest statement

The human CHIKV antibodies described herein are the subject of a U. S. patent application filed by the Albert Einstein College of Medicine. M.S.D. is a consultant for Inbios and Sanofi-Pasteur and on the Scientific Advisory Board of Moderna. M.J.A. owns stocks and F.W.H. and S.S. own stock options in Integrated Biotherapeutics.

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