Exploiting the reverse vaccinology approach to design novel subunit vaccines against Ebola virus.

Abstract

Ebola virus is a highly pathogenic RNA virus that causes the Ebola haemorrhagic fever in human. This virus is considered as one of the dangerous viruses in the world with very high mortality rate. To date, no epitope-based subunit vaccine has yet been discovered to fight against Ebola although the outbreaks of this deadly virus took many lives in the past. In this study, approaches of reverse vaccinology were utilized in combination with different tools of immunoinformatics to design subunit vaccines against Ebola virus strain Mayinga-76. Three potential antigenic proteins of this virus i.e., matrix protein VP40, envelope glycoprotein and nucleoprotein were selected to construct the subunit vaccine. The MHC class-I, MHC class-II and B-cell epitopes were determined initially and after some robust analysis i.e., antigenicity, allergenicity, toxicity, conservancy and molecular docking study, EV-1, EV-2 and EV-3 were constructed as three potential vaccine constructs. These vaccine constructs are also expected to be effective on few other strains of Ebola virus since the highly conserved epitopes were used for vaccine construction. Thereafter, molecular docking study was conducted on these vaccines and EV-1 emerged as the best vaccine construct. Afterward, molecular dynamics simulation study revealed the good performances and stability of the intended vaccine protein. Finally, codon adaptation and in silico cloning were carried out to design a possible plasmid (pET-19b plasmid vector was used) for large scale production of the EV-1 vaccine. However, further in vitro and in vivo studies might be required on the predicted vaccines for final validation.