Kim, Arthur S. and Kafai, Natasha M. and Winkler, Emma S. and Gilliland, Theron C. Jr Jr and Cottle, Emily L. and Earnest, James T. and Jethva, Prashant N. and Kaplonek, Paulina and Shah, Aadit P. and Fong, Rachel H. and Davidson, Edgar and Malonis, Ryan J. and Quiroz, Jose A. and Williamson, Lauren E. and Vang, Lo and Mack, Matthias and Crowe, James E. Jr Jr and Doranz, Benjamin J. and Lai, Jonathan R. and Alter, Galit and Gross, Michael L. and Klimstra, William B. and Fremont, Daved H. and Diamond, Michael S. (2021) Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope. CELL, 184 (17). 4414-+. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)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 protectsmice against infection by both arthritogenic (chikungunya andMayaro) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EQUINE ENCEPHALITIS-VIRUS; NEUTRALIZING MONOCLONAL-ANTIBODIES; INFECTIOUS CDNA-CLONES; SEMLIKI-FOREST-VIRUS; CHIKUNGUNYA VIRUS; SINDBIS VIRUS; HEPARAN-SULFATE; ENCEPHALOMYELITIS VIRUS; EFFECTOR FUNCTIONS; WILD-TYPE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 12:12 |
| Last Modified: | 27 Sep 2022 12:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48072 |
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