Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein
| Autor: | Arthur S. Kim, S. Kyle Austin, Derek W. Trobaugh, Mark K. Slifka, Lauren E. Williamson, Daved H. Fremont, Michael S. Diamond, Adam Zuiani, Douglas S. Reed, Chengqun Sun, Christina L. Gardner, James E. Crowe, William B. Klimstra, Katherine Basore |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Microbiology (medical)
Encephalomyelitis Equine Eastern equine encephalitis virus medicine.drug_class Immunology Alphavirus medicine.disease_cause Monoclonal antibody Antibodies Viral Applied Microbiology and Biotechnology Microbiology Epitope Neutralization Article 03 medical and health sciences Epitopes Mice Protein Domains Viral Envelope Proteins Cricetinae Chlorocebus aethiops Genetics medicine Animals Humans Vero Cells 030304 developmental biology 0303 health sciences biology 030306 microbiology Antibodies Monoclonal Cell Biology biology.organism_classification Virology Antibodies Neutralizing 3. Good health Epitope mapping HEK293 Cells Vero cell biology.protein Encephalitis Virus Eastern Equine Female Antibody Epitope Mapping |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | 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 (EC50 and EC99) 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. |
| Databáze: | OpenAIRE |
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