期刊
CELL
卷 183, 期 7, 页码 1884-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.11.011
关键词
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资金
- U-M Life Sciences Institute
- U-M Biosciences Initiative
- NIH [S10OD020011, T32 HL069765, F31 AI145189, U19 AI142790, R01 AI095436]
- U.S. Defense Threat Reduction Agency [HDTRA1-13-10034, HDTRA1-15-1-0047]
- U.S. NCATS [CTSA UL1 TR002243]
Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has recently shown an increase in human cases. Here, we characterize human monoclonal antibodies (mAbs) isolated from a survivor of natural EEEV infection with potent (<20 pM) inhibitory activity of EEEV Cryo-electron microscopy reconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solved in complex with chimeric Sindbis/EEEV virions to 7.2 angstrom and 8.3 angstrom, respectively. The mAbs recognize two distinct antigenic sites that are critical for inhibiting viral entry into cells. EEEV-33 and EEEV-143 protect against disease following stringent lethal aerosol challenge of mice with highly pathogenic EEEV. These studies provide insight into the molecular basis for the neutralizing human antibody response against EEEV and can facilitate development of vaccines and candidate antibody therapeutics.
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