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
