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Cited by 54Mosquito-borne diseases and controlViral Infections and VectorsSARS-CoV-2 and COVID-19 Research

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

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Kim, Arthur S., Austin, S. Kyle, Gardner, Christina L., Zuiani, Adam, Reed, Douglas S., Trobaugh, Derek W., Sun, Chengqun, Basore, Katherine +6 more·2018·Nature Microbiology
DOI 10.1038/s41564-018-0286-4PMC PMC6294662
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Abstract

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.

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  • The insertion of GFP into the chimeric SINV-VEEV virus has minimal effects on virus infection and replication.

    “The insertion of GFP has minimal effects on virus infection and replication20,24.”

    From LDLRAD3 is a receptor for Venezuelan equine encephalitis virus (2020) · cites this paper as [24]

    The Results section (‘Generation of anti-EEEV mAbs’; page unavailable) says that a SINV-EEEV chimera replicated efficiently in cell culture. The Methods section (‘Cell lines and plasmids’; page unavailable) describes that chimera, but neither passage addresses GFP insertion into SINV-VEEV or its effects on infection and replication. Searches for GFP insertion and a fluorescent reporter found no passage that settles the claim. (LLM, conf=0.76)

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References 53 · Cited by 54

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Authors
Kim, A. S., Austin, S. K., Gardner, C. L., Zuiani, A., Reed, D. S., Trobaugh, D. W., Sun, C., Basore, K., Williamson, L. E., Crowe, J. E., Slifka, M. K., Fremont, D. H., Klimstra, W. B., & Diamond, M. S.
Affiliations
  • Washington University in St. Louis (US)
  • University of Pittsburgh (US)
  • Vanderbilt University Medical Center (US)
  • Oregon National Primate Research Center (US)
Corresponding author
Diamond, Michael S.
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2018-11-19
Volume
4
Issue
1
Pages
187-197
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-018-0286-4
PMC
PMC6294662
OpenAlex
W2900372023
Cited by
54
References
53
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 9 · 2019: 2 · 2018: 1
FWCI
5.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (HDTRA1-13-1-0034, P51OD011092)
  • Defense Threat Reduction Agency (HDTRA1-13-1-0034, HDTRA1-15-1-0013, HDTRA1)
  • National Institute of Allergy and Infectious Diseases (R01AI095436)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
eastern equine encephalitis virus, E2 glycoprotein, neutralizing monoclonal antibodies, epitope mapping, alanine scanning, alphavirus, biodefense, vaccine design
MeSH terms
Protein Domains, Animals, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Chlorocebus aethiops, Encephalitis Virus, Eastern Equine, Encephalomyelitis, Equine, Female, Cricetinae, Humans, Vero Cells, Viral Envelope Proteins, Epitope Mapping, Mice, Antibodies, Neutralizing, HEK293 Cells

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