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Hum Vaccin Immunother. 2017 Dec 2;13(12):2953-2966. doi: 10.1080/21645515.2017.1360454. Epub 2017 Sep 18.

Combinatorial peptide-based epitope mapping from Ebola virus DNA vaccines and infections reveals residue-level determinants of antibody binding.

Author information

1
a Biotechnology HPC Software Applications Institute , Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick , MD , USA.
2
b US Army Medical Research Institute of Infectious Diseases, Fort Detrick , MD , USA.

Abstract

Ebola virus (EBOV) infection is highly lethal and results in severe febrile bleeding disorders that affect humans and non-human primates. One of the therapeutic approaches for treating EBOV infection focus largely on cocktails of monoclonal antibodies (mAbs) that bind to specific regions of the EBOV glycoprotein (GP) and neutralize the virus. Recent structural studies using cryo-electron microscopy have identified key epitopes for several EBOV mAbs. While such information has yielded deep insights into antibody binding, limitations on resolution of these structures often preclude a residue-level analysis of EBOV epitopes. In this study, we performed combinatorial peptide-based epitope mapping of EBOV GP against a broad panel of mAbs and polyclonal sera derived from several animal species vaccinated with EBOV DNA and replicon vaccines and/or exposed to EBOV infection to identify residue-level determinants of antibody binding. The peptide-based epitope mapping obtained from a wide range of serum and mAb samples, combined with available cryo-EM structure reconstructions revealed fine details of antibody-virus interactions, allowing for a more precise and comprehensive mapping of antibody epitopes on EBOV GP. We show how these residue-level epitope definitions can be used to characterize antigenic variation across different filoviruses, and provide a theoretical basis for predicting immunity and cross-neutralization in potential future outbreaks.

KEYWORDS:

Ebola glycoprotein; dna vaccine; ebola antibody; ebolaviruses; epitope mapping

PMID:
28922082
PMCID:
PMC5718834
DOI:
10.1080/21645515.2017.1360454
[Indexed for MEDLINE]
Free PMC Article

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