Immunoinformatic Aided Design of a Potential Multiepitopic Vaccine against Neisseria gonorrhoeae Infections

Abstract

Gram-negative, obligate pathogen Neisseria gonorrhoeae is the second most prevalent cause of sexually transmitted bacterial diseases, globally. It is known to cause high morbidity with reproductive and obstetrics complications. Moreover, numerous scientific reports have described N. gonorrhoeae to be one of the top multi drug resistant organism. In the event of resistance development towards the last-resort antibiotics, its treatment has become almost impossible due to the sweeping decline in the availability of therapeutic possibilities. Despite numerous vaccine candidates being proposed, no marketable vaccine for this ubiquitous pathogen is available. It is therefore apropos to formulate a rational vaccine plan to get rid of the super-bug. Considering the global scale of Neisseria gonorrhoeae infection, we methodically combined the most conserved epitopes from all completely assembled strains with the help of different immunoinformatic approaches to envisage a systematic multi-epitope vaccine design. The proposed vaccine contains highly immunogenic, non-allergenic and non-cytotoxic epitopes with high affinity for B-cells, Cytotoxic T cells and Helper T cells. The finalized epitopes proved to be significant as they are exclusive to Neisseria gonorrhoeae and contain no homology with the commensal species of Neisseria as well as any human protein. The 3-D structure of the construct was projected, refined, and validated by employing several in-silico approaches. The molecular docking results suggest that the vaccine construct is suitable for binding to the TLR-2 receptor. The stable and flexible binding of the vaccine construct with the TLR-2 receptor was confirmed through molecular dynamics and normal mode analysis. Moreover, the In-silico immune simulation analysis has revealed that the vaccine has stimulated a prominent increase in the levels of antibodies, Cytotoxic and Helper T-cells, dendritic cells and macrophages. Thus, the vaccine is well adapted to show innate and adaptive immune response. The proposed vaccine model also fulfills all the physiochemical criteria for a good vaccine design as it is thermostable, immunogenic, water-soluble, and non-allergenic