AUTHOR=Shey Robert Adamu , Ghogomu Stephen Mbigha , Nebangwa Derrick Neba , Shintouo Cabirou Mounchili , Yaah Ntang Emmaculate , Yengo Bernis Neneyoh , Nkemngo Francis Nongley , Esoh Kevin Kum , Tchatchoua Nelly Manuela Tatchou , Mbachick Tekoh Terriss , Dede Api Fon , Lemoge Arnaud Azonpi , Ngwese Roland Akwelle , Asa Bertha Fru , Ayong Lawrence , Njemini Rose , Vanhamme Luc , Souopgui Jacob TITLE=Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins JOURNAL=Frontiers in Tropical Diseases VOLUME=3 YEAR=2022 URL=https://www.frontiersin.org/journals/tropical-diseases/articles/10.3389/fitd.2022.1046522 DOI=10.3389/fitd.2022.1046522 ISSN=2673-7515 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 14 O. 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. The Mycobacterium tuberculosis Resuscitation-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 against O. volvulus infection. 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.