Pioneered by Rappuoli and colleagues, reverse vaccinology—which initially included genome and later proteome mining—has proven to be very successful in the discovery of vaccine candidates against many pathogenic bacteria (12– 15). In particular, these methodologies paved the way for the newly developed group B meningococcal vaccine, which was a formidable effort for many years. Among the 28 antigens that were discovered and that elicited bactericidal antibodies against group B meningococci in vitro were the Neisserial heparin-binding antigen (NHBA), factor H-binding protein (fHbp), and the Neisserial adhesin A (NadA). These three proteins are formulated as part of the Bexsero meningococcal group B vaccine approved by the European commission in 2013 and the United States in February of 2015 (12, 15, 16). Unfortunately, N. gonorrhoeae homologs of these proteins are not suitable vaccine targets (17). Further, in contrast to meningococcal vaccines, progress on gonococcal vaccines has been hampered primarily by the absence of a vaccine-targetable surface capsule, exceptional variability of several surface antigens, a poor understanding of protective responses, and until relatively recently, the lack of a small laboratory animal model to systematically test potential vaccine candidates (16). However, recent potential breakthroughs—such as the availability of transgenic mice to alleviate some host restrictions, new insights into immunosuppression mechanisms used by N. gonorrhoeae, and growing evidence that induction of Th1 response may be critical for vaccine efficacy—justify re-visiting gonorrhea vaccine development and initiating a significant focus in this area (16, 18–20).
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