Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses

Ryan J. Malonis, James T. Earnest, Arthur S. Kim, Matthew Angeliadis, Frederick W. Holtsberg, M. Javad Aman, Rohit Jangra, Kartik Chandran, Johanna P. Daily, Michael S. Diamond, Margaret Kielian, Jonathan R. Lai

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Arthritogenic alphaviruses are globally distributed, mosquitotransmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibodymediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline-revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the crossreactive and cross-protective antibody response to human alphavirus infections.

Original languageEnglish (US)
Article numbere2100104118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number37
DOIs
StatePublished - Sep 14 2021

Keywords

  • Alphaviruses
  • Broadly neutralizing antibodies
  • Heterologous immunity
  • Mayaro virus
  • Monoclonal antibodies

ASJC Scopus subject areas

  • General

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