Recently, Shewell et al. demonstrated that deletion of the glycosylated immunodominant C-terminus of AniA produced a truncated protein that elicited antibodies that inhibited nitrite reductase activity [69]. Vaccine-mediated inhibition of AniA function may be an effective approach because the capacity to grow anaerobically is likely an important adaptation during infection of the genital tract where oxygen tension is reduced. This hypothesis is supported by the detection of AniA-specific antibodies from women with lower or upper genital tract

infections and one patient with DGI [70]. AniA is also required for mature biofilm formation, which may protect against innate defenses Cilengitide in vivo [71]. The exciting development of group B meningococcal vaccines, which was a formidible challenge for many years, may provide a useful template for developing a gonorrhea vaccine [72], [73] and [74]. Some of these vaccines contain outer membrane vesicles (OMV) and some are genetically engineered to stabilize the expression

of phase variable antigens and increase the range of antigenic specificities. Detergent-treated OMVs or OMVs produced from LOS mutants have been used to diminish endotoxicity. Immunization and challenge studies with Gc OMV have not been reported; a Gc outer membrane protein preparation demonstrated protection in mice when delivered intranasally mTOR inhibitor with CT [54], but this approach was not successful in subsequent studies, possibly due to differences in the protein isolation methods used [35]. The Novartis 4CmenB vaccine consists of OMVs combined with the NadA protein and two fusion proteins, factor H-binding

protein (fHbp) and neisserial heparin binding antigen (NHBA) fused to two other conserved antigens [74]. None of the three proteins (fHBP, NHBA and NadA) in the 4CmenB vaccine [74] are predicted to be suitable vaccine targets for Gc [75]; however, gonorrhea research may benefit from the use of proteomics technology and, or genome mining, which have advanced medroxyprogesterone the development of vaccines for group B N. meningitidis. Immunization of the genital tract also challenges gonorrhea vaccine development, although we are encouraged by the success of the HPV vaccine. Most efforts to develop a vaccine against gonorrhea have focused on conventional parenteral immunization, which generates circulating, predominantly IgG antibodies, but is generally ineffective at inducing secretory (S) IgA at mucosal surfaces. However, the genital tract secretions of both males and females contain more IgG derived largely from the circulation than SIgA produced locally and transported through epithelial cells [57].