Progress Toward a Gonococcal Vaccine: The Way Forward

Abstract

The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of Neisseria gonorrhoeae that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully developed for human use, leading to pessimism over whether this goal was actually attainable. Several factors have contributed to this situation, including extensive variation of the expression and specificity of many of the gonococcal surface antigens, and the ability of N. gonorrhoeae to resist destruction by complement and other innate immune defense mechanisms. The natural host restriction of N. gonorrhoeae for humans, coupled with the absence of any definable state of immunity arising from an episode of gonorrhea, have also complicated efforts to study gonococcal pathogenesis and the host's immune responses. However, recent findings have elucidated how the gonococcus exploits and manipulates the host's immune system for its own benefit, utilizing human-specific receptors for attachment to and invasion of tissues, and subverting adaptive immune responses that might otherwise be capable of eliminating it. While no single experimental model is capable of providing all the answers, experiments utilizing human cells and tissues in vitro, various in vivo animal models, including genetically modified strains of mice, and both experimental and observational human clinical studies, have combined to yield important new insight into the immuno-pathogenesis of gonococcal infection. In turn, these have now led to novel approaches for the development of a gonococcal vaccine. Ongoing investigations utilizing all available tools are now poised to make the development of an effective human vaccine against gonorrhea an achievable goal within a foreseeable time-frame.

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae

“…Similarities between human and experimental murine infection include the fact that mice, like humans, produce a transient and unremarkable humoral response to Ng infection and can be reinfected with the same strain. Ng induces the Th17 pathway in both humans [19, 20] and mice [58, 59], which leads to recruitment of PMNs to the infection site. Similar to that reported for human cervical infections, hormonally driven, cyclical fluctuations in Ng colonization load and selection for Opa protein phase variants occurs over the course of murine infection [60].…”

“…There is little immunity to natural infection in humans and mice [18], and there is growing evidence that the adaptive response to Ng infection is suppressed. As recently reviewed by Lovett and Duncan [19], human humoral immune responses to Ng to infection are modest at best and the analysis thereof is complicated by pre-existing antibodies to carbohydrate and protein surface antigens that are induced by commensal Neisseria sp ., although antibodies to some antigens are increased by infection [20]. Human cellular responses to Ng infection are less well studied, but appear to be driven by a Th17 pro-inflammatory response.…”

“…Human cellular responses to Ng infection are less well studied, but appear to be driven by a Th17 pro-inflammatory response. Th1 responses, in contrast, appear suppressed [20], and several pathways that result in reduced antigen presentation and, or inhibition of T cell responses to Ng have been identified using human immune cells and experimentally infected mice [21-25].…”

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae

“…Human cellular responses to Ng infection are less well studied, but appear to be driven by a Th17 pro-inflammatory response. Th1 responses, in contrast, appear suppressed [20], and several pathways that result in reduced antigen presentation and, or inhibition of T cell responses to Ng have been identified using human immune cells and experimentally infected mice [21][22][23][24][25].…”

Neisseria gonorrhoeae NGO2105 Is an Autotransporter Protein Involved in Adhesion to Human Cervical Epithelial Cells and in vivo Colonization

“…Therefore, N. gonorrhoeae was listed as an "urgent threat event" by the World Health Organization (WHO) (Blomquist et al, 2014). For these reasons, the search for effective treatment strategies, such as new drugs and vaccines, has become more urgent (Russell et al, 2019). Further exploration of the pathogenic molecules of gonorrhoeae has become even more important for the development of new therapeutic targets.…”