Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

Scott A. Smith, Laurie A. Silva, Julie M. Fox, Andrew I. Flyak, Nurgun Kose, Gopal Sapparapu, Solomiia Khomandiak, Alison W. Ashbrook, Kristen M. Kahle, Rachel H. Fong, Sherri Swayne, Benjamin J. Doranz, Charles E. McGee, Mark T. Heise, Pankaj Pal, James D. Brien, S. Kyle Austin, Michael S. Diamond, Terence S. Dermody, James E. Crowe

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure- based vaccine development.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalCell Host and Microbe
Volume18
Issue number1
DOIs
StatePublished - 2015

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