Vaccines against gonorrhea: Current status and future challenges

Abstract

Gonorrhea occurs at high incidence throughout the world and significantly impacts reproductive health and the spread of human immunodeficiency virus. Current control measures are inadequate and seriously threatened by the rapid emergence of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however, recent advances justify significant effort in this area. Conserved vaccine antigens have been identified that elicit bactericidal antibodies and, or play key roles in pathogenesis that could be targeted by a vaccine-induced response. A murine genital tract infection model is available for systematic testing of antigens, immunization routes and adjuvants, and transgenic mice exist to relieve some host restrictions. Furthermore, mechanisms by which N. gonorrhoeae avoids inducing a protective adaptive response are being elucidated using human cells and the mouse model. Induction of a Th1 response in mice clears infection and induces a memory response, which suggests Th1-inducing adjuvants may be key in vaccine-induced protection. Continued research in this area should include human testing and clinical studies to confirm or negate findings from experimental systems and to define protective host factors.

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea

“…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).…”

“…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).…”

“…Currently, ϳ12 potential gonorrhea vaccine antigens are being pursued (16). However, this is a very limited repertoire considering that, during the development of the Bexsero vaccine, out of nearly 600 candidates selected by in silico analysis, 350 recombinant meningococcal proteins were successfully expressed in Escherichia coli and evaluated for their surface exposure and ability to induce bactericidal antibodies (12).…”

Neisseria gonorrhoeae Evades Calprotectin-Mediated Nutritional Immunity and Survives Neutrophil Extracellular Traps by Production of TdfH

“…Recent studies have also demonstrated that the gonococcus proactively skews the host response away from humoral immunity and toward innate immunity, which is to the pathogen's advantage (9). New vaccine development strategies will likely include immunomodulatory therapy along with presentation of conserved surface antigens in an effort to develop a protective response (10). Thus, the identification of potential vaccine targets remains imperative.…”

A Thermonuclease ofNeisseria gonorrhoeaeEnhances Bacterial Escape From Killing by Neutrophil Extracellular Traps

“…Gonorrhea can cause acute urethritis in males and cervicitis in females and lead to sequelae such as pelvic inflammatory syndrome, ectopic pregnancy, sterility, and, through vertical transmission, infant blindness [2]. There is no vaccine for gonorrhea, and antibiotic-resistant N. gonorrhoeae strains are emerging, raising global public health concern [3,4].…”