Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice

ABSTRACT

We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed 2 DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.

KEYWORDS:

• Ebola virus
• filovirus
• DNA vaccine
• epitope mapping
• antibody
• focusing
• mice

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

Support for this research was provided by the Joint Science and Technology Office of the Defense Threat Reduction Agency, the Military Infectious Diseases Research Program of the United States (US) Army Medical Research and Materiel Command and the US Department of Defense (DoD) High-Performance Computing Modernization Program. These studies were performed while DM held a National Research Council Postdoctoral Fellowship at USAMRIID. The opinions, interpretations, conclusions, and recommendations contained herein are those of the authors and are not necessarily endorsed by the US. Army.