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

• DOI: 10.1371/journal.ppat.1008061
• Publication Date: 2019-11-07T18:27:23Z
• Authors: Jose A. Quiroz; Ryan J. Malonis; Larissa B. Thackray; Courtney A. Cohen; Jesper Pallesen; Rohit K. Jangra; Rebecca S. Brown; Daniel Hofmann; Frederick W. Holt...; Sergey Shulenin; Elisabeth K. Nyak...; Lorellin A. Durnell; Vinayak Rayannavar; Johanna P. Daily; Andrew B. Ward; M. Javad Aman; John M. Dye; Kartik Chandran; Michael S. Diamond; Margaret Kielian; Jonathan R. Lai
• Keywords: Conformational epitope; Epitope mapping

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