Identification of peptides containing epitopes of Ebola virus eliciting immune response

Abstract

Last 5 years have witnessed two of the worst Ebola virus outbreaks in history which have resulted in significant morbidity and mortality. Rapid spread of the virus across the globe has raised concerns over the safety of world citizens. No licensed vaccine or drug protective against human infecting Ebola species is available as yet. In a panic driven step, incompletely tested vaccines have been approved along with antiviral prophylaxis to counter unforeseen outbreaks. However, production difficulties, safety concerns, high booster dosage requirement, inefficient delivery systems and pre-existing immunity are some of the challenges faced by current vaccine development approaches. Hence, there is a pressing need to develop a vaccine strategy which can offer universal or at least broad protection against current and future Ebola virus strains in populations distributed worldwide. Highly conserved peptide fragments belonging to critical viral proteins and containing multiple epitopes which have the capacity to interact with a wide array of HLA molecules are anticipated to serve as potent candidates for a universal or broadly reactive Ebola vaccine. In light of the above facts, the present study is oriented towards identifying highly conserved promiscuous peptides containing multiple overlapping T (CD8+ and CD4+) and B cell epitopes and devoid of undesirable responses (autoimmunity, toxicity and allergenicity) in glycoprotein (GP) and nucleoprotein (NP) of Ebola virus using immunoinformatics techniques such as epitope prediction tools, HLA and population coverage analysis and molecular docking. Further, peripheral blood mononuclear cells (PBMC) from healthy volunteers were subjected to repetitive stimulation by peptides that presented the best in silico results to assess their immunogenic response by measuring cell proliferation and IFN-and#947; production with the help of MTT and ELISA assays respectively.