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


Autoři: Jose A. Quiroz aff001;  Ryan J. Malonis aff001;  Larissa B. Thackray aff002;  Courtney A. Cohen aff003;  Jesper Pallesen aff004;  Rohit K. Jangra aff005;  Rebecca S. Brown aff006;  Daniel Hofmann aff001;  Frederick W. Holtsberg aff007;  Sergey Shulenin aff007;  Elisabeth K. Nyakatura aff001;  Lorellin A. Durnell aff002;  Vinayak Rayannavar aff001;  Johanna P. Daily aff008;  Andrew B. Ward aff004;  M. Javad Aman aff007;  John M. Dye aff003;  Kartik Chandran aff005;  Michael S. Diamond aff002;  Margaret Kielian aff006;  Jonathan R. Lai aff001
Působiště autorů: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America aff001;  Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America aff002;  Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America aff003;  Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America aff004;  Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America aff005;  Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America aff006;  Integrated Biotherapeutics Inc., Rockville, Maryland, United States of America aff007;  Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America aff008;  Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America aff009;  Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America aff010
Vyšlo v časopise: Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008061
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008061

Souhrn

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.

Klíčová slova:

Antibodies – Enzyme-linked immunoassays – Chikungunya infection – Immunoprecipitation – Microbial mutation – Viral structure – Chikungunya virus – Viral entry


Zdroje

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Hygiena a epidemiologie Infekční lékařství Laboratoř

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