The mechanistic basis of protection by non-neutralizing anti-alphavirus antibodies

James T. Earnest, Autumn C. Holmes, Katherine Basore, Matthias Mack, Daved H. Fremont, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Although neutralizing monoclonal antibodies (mAbs) against epitopes within the alphavirus E2 protein can protect against infection, the functional significance of non-neutralizing mAbs is poorly understood. Here, we evaluate the activity of 13 non-neutralizing mAbs against Mayaro virus (MAYV), an emerging arthritogenic alphavirus. These mAbs bind to the MAYV virion and surface of infected cells but fail to neutralize infection in cell culture. Mapping studies identify six mAb binding groups that localize to discrete epitopes within or adjacent to the A domain of the E2 glycoprotein. Remarkably, passive transfer of non-neutralizing mAbs protects against MAYV infection and disease in mice, and their efficacy requires Fc effector functions. Monocytes mediate the protection of non-neutralizing mAbs in vivo, as Fcγ-receptor-expressing myeloid cells facilitate the binding, uptake, and clearance of MAYV without antibody-dependent enhancement of infection. Humoral protection against alphaviruses likely reflects contributions from non-neutralizing antibodies through Fc-dependent mechanisms that accelerate viral clearance.

Original languageEnglish
Article number108962
JournalCell Reports
Volume35
Issue number1
DOIs
StatePublished - Apr 6 2021

Keywords

  • Fc effector
  • alphavirus
  • antibody
  • epitope
  • mapping
  • monocytes
  • neutralization
  • pathogenesis
  • protection

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