Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope

Arthur S. Kim, Natasha M. Kafai, Emma S. Winkler, Theron C. Gilliland, Emily L. Cottle, James T. Earnest, Prashant N. Jethva, Paulina Kaplonek, Aadit P. Shah, Rachel H. Fong, Edgar Davidson, Ryan J. Malonis, Jose A. Quiroz, Lauren E. Williamson, Lo Vang, Matthias Mack, James E. Crowe, Benjamin J. Doranz, Jonathan R. Lai, Galit AlterMichael L. Gross, William B. Klimstra, Daved H. Fremont, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Alphaviruses are emerging, mosquito-transmitted pathogens that cause musculoskeletal and neurological disease in humans. Although neutralizing antibodies that inhibit individual alphaviruses have been described, broadly reactive antibodies that protect against both arthritogenic and encephalitic alphaviruses have not been reported. Here, we identify DC2.112 and DC2.315, two pan-protective yet poorly neutralizing human monoclonal antibodies (mAbs) that avidly bind to viral antigen on the surface of cells infected with arthritogenic and encephalitic alphaviruses. These mAbs engage a conserved epitope in domain II of the E1 protein proximal to and within the fusion peptide. Treatment with DC2.112 or DC2.315 protects mice against infection by both arthritogenic (chikungunya and Mayaro) and encephalitic (Venezuelan, Eastern, and Western equine encephalitis) alphaviruses through multiple mechanisms, including inhibition of viral egress and monocyte-dependent Fc effector functions. These findings define a conserved epitope recognized by weakly neutralizing yet protective antibodies that could be targeted for pan-alphavirus immunotherapy and vaccine design.

Original languageEnglish (US)
Pages (from-to)4414-4429.e19
JournalCell
Volume184
Issue number17
DOIs
StatePublished - Aug 19 2021

Keywords

  • alphavirus
  • antibody
  • arthritis
  • encephalitis
  • Fc effector
  • immunity
  • inhiibtion
  • mice
  • pathogenesis
  • protection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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