Earnest, James T. and Holmes, Autumn C. and Basore, Katherine and Mack, Matthias and Fremont, Daved H. and Diamond, Michael S. (2021) The mechanistic basis of protection by non-neutralizing anti-alphavirus antibodies. CELL REPORTS, 35 (1): 108962. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)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-neutralizingmAbs 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 Fcg-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2022 06:32 |
| Last Modified: | 23 Sep 2022 06:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47914 |
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