Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection.

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 Å and 8.3 Å, 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.
Competing Interests: Declaration of Interests M.S.D. is consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals, is on the Scientific Advisory Boards of Moderna and Immunome, and is a recipient of grants from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as consultant for Eli Lilly and Sanofi, is on Scientific Advisory Boards of CompuVax and Meissa Vaccines, is recipient of research grants from Moderna and Sanofi, and is Founder of IDBiologics, Inc. Vanderbilt University has applied for patents that are related to this work.
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