Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins

Abstract

Almost a decade ago, it was recognized that the global elimination of onchocerciasis by 2030 will not be feasible without, at least, an effective prophylactic and/or therapeutic vaccine to complement chemotherapy and vector control strategies. Recent advances in computational immunology (immunoinformatics) have seen the design of novel multi-epitope onchocerciasis vaccine candidates which are however yet to be evaluated in clinical settings. Still, continued research to increase the pool of vaccine candidates, and therefore the chance of success in a clinical trial remains imperative. Here, we designed a multi-epitope vaccine candidate by assembling peptides from 14O. volvulus(Ov) proteins using an immunoinformatics approach. An initial 126 Ov proteins, retrieved from the Wormbase database, and at least 90% similar to orthologs in related nematode species of economic importance, were screened for localization, presence of transmembrane domain, and antigenicity using different web servers. From the 14 proteins retained after the screening, 26 MHC-1 and MHC-II (T-cell) epitopes, and linear B-lymphocytes epitopes were predicted and merged using suitable linkers. TheMycobacterium tuberculosisResuscitation-promoting factor E (RPFE_MYCTU), which is an agonist of TLR4, was then added to the N-terminal of the vaccine candidate as a built-in adjuvant. Immune simulation analyses predicted strong B-cell and IFN-γ based immune responses which are necessary for protection againstO. volvulusinfection. Protein-protein docking and molecular dynamic simulation predicted stable interactions between the 3D structure of the vaccine candidate and human TLR4. These results show that the designed vaccine candidate has the potential to stimulate both humoral and cellular immune responses and should therefore be subject to further laboratory investigation.