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Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein
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Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein
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Journal Article
Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein
2019
Overview
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
50
and EC
99
) of less than 10 and 100 ng ml
−1
, 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.
Neutralizing murine monoclonal antibodies against the Eeastern equine encephalitis virus target the E2 glycoprotein, block infection at a post-attachment stage by inhibiting viral membrane fusion and protect mice from lethal challenge.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 96/106
/ Aerosols
/ Alanine
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Biomedical and Life Sciences
/ Encephalitis Virus, Eastern Equine - immunology
/ Encephalomyelitis, Equine - immunology
/ Encephalomyelitis, Equine - prevention & control
/ Encephalomyelitis, Equine - virology
/ Female
/ Horses
/ Humans
/ Mice
/ Protein Domains - immunology
/ Viral Envelope Proteins - immunology
/ Virology
/ Viruses
