National Academy of Sciences, Proceedings of the National Academy of Sciences, 37(118), 2021
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Significance Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and Mayaro virus (MAYV), cause febrile illness, rash, and a debilitating chronic polyarthritis in humans. Currently, there are no approved vaccines or antiviral therapies for the prevention or treatment of alphavirus infection. Here, we identified and characterized 33 monoclonal antibodies (mAbs) from a CHIKV-convalescent donor that cross-react with other arthritogenic alphaviruses. We demonstrate that five broadly neutralizing mAbs can inhibit multiple arthritogenic alphaviruses and map their epitopes through binding and viral escape mutant analysis. Finally, we show that two mAbs, DC2.M16 and DC2.M357, protect against alphavirus disease in mice. These studies inform our understanding of how the human immune system combats alphavirus infection and may guide the development of antiviral treatments and vaccines.