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J Exp Med. 2019 Jul 23. pii: jem.20190736. doi: 10.1084/jem.20190736. [Epub ahead of print]

Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity.

Author information

1
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
3
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA.
4
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.
5
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO.
6
Department of Medicine, Washington University School of Medicine, St. Louis, MO diamond@wusm.wustl.edu.
7
The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO.

Abstract

Despite causing outbreaks of fever and arthritis in multiple countries, no countermeasures exist against Mayaro virus (MAYV), an emerging mosquito-transmitted alphavirus. We generated 18 neutralizing mAbs against MAYV, 11 of which had "elite" activity that inhibited infection with EC50 values of <10 ng/ml. Antibodies with the greatest inhibitory capacity in cell culture mapped to epitopes near the fusion peptide of E1 and in domain B of the E2 glycoproteins. Unexpectedly, many of the elite neutralizing mAbs failed to prevent MAYV infection and disease in vivo. Instead, the most protective mAbs bound viral antigen on the cell surface with high avidity and promoted specific Fc effector functions, including phagocytosis by neutrophils and monocytes. In subclass switching studies, murine IgG2a and humanized IgG1 mAb variants controlled infection better than murine IgG1 and humanized IgG1-N297Q variants. An optimally protective antibody response to MAYV and possibly other alphaviruses may require tandem virus neutralization by the Fab moiety and effector functions of the Fc region.

PMID:
31337735
DOI:
10.1084/jem.20190736

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