James Crowe
Faculty Member
Last active: 3/31/2019

Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein.

Kim AS, Austin SK, Gardner CL, Zuiani A, Reed DS, Trobaugh DW, Sun C, Basore K, Williamson LE, Crowe JE, Slifka MK, Fremont DH, Klimstra WB, Diamond MS
Nat Microbiol. 2019 4 (1): 187-197

PMID: 30455470 · PMCID: PMC6294662 · DOI:10.1038/s41564-018-0286-4

Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus with a high case mortality rate in humans. EEEV is a biodefence concern because of its potential for aerosol spread and the lack of existing countermeasures. Here, we identify a panel of 18 neutralizing murine monoclonal antibodies (mAbs) against the EEEV E2 glycoprotein, several of which have 'elite' activity with 50 and 99% effective inhibitory concentrations (EC and EC) of less than 10 and 100 ng ml, respectively. Alanine-scanning mutagenesis and neutralization escape mapping analysis revealed epitopes for these mAbs in domains A or B of the E2 glycoprotein. A majority of the neutralizing mAbs blocked infection at a post-attachment stage, with several inhibiting viral membrane fusion. Administration of one dose of anti-EEEV mAb protected mice from lethal subcutaneous or aerosol challenge. These experiments define the mechanistic basis for neutralization by protective anti-EEEV mAbs and suggest a path forward for treatment and vaccine design.

MeSH Terms (17)

Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Cercopithecus aethiops Cricetinae Encephalitis Virus, Eastern Equine Encephalomyelitis, Equine Epitope Mapping Epitopes Female HEK293 Cells Humans Mice Protein Domains Vero Cells Viral Envelope Proteins

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