Gonococcal Vaccine Development: Lessons from Group B Meningococcal Vaccines

A retrospective case-control study, published online in The Lancet on July 10, 2017, reported that MeNZB–a group B meningococcal vaccine– was effective for preventing gonorrhea acquisition. The vaccine was administered to about 1 million adolescents in New Zealand between 2004 and 2006, and gonorrhea cases fell 31% in those vaccinated compared to unvaccinated controls. The exact mechanisms by which MeNZB, which contains outer membrane vesicles (OMVs) from Neisseria meningitidis group B strain NZ98/254, provided crossprotection against gonorrhea remain to be elucidated. Gonorrhea is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae, a close relative of N. meningitidis with 80-90% genetic homology. The WHO estimates that approximately 78 million new cases of gonorrhea occur annually, half of which are in lowand middle-income countries. Untreated infection can lead to complications, such as pelvic inflammatory disease, infertility and ectopic pregnancy in women, and urethritis and infertility in men. Gonorrhea also increases the risk of acquiring and transmitting HIV. Since the first introduction of antibiotics for gonorrhea treatment in themid-1930s, the bacterium has demonstrated a remarkable ability to develop resistance to antibiotics through a variety of mechanisms, due to its natural competence in DNA exchange. Some countries have reported cases of gonorrhea that are resistant to all known antibiotics. On July 7, 2017, the WHO issued a warning of the rise in untreatable antibiotic-resistant gonorrhea, and called for new drugs to be developed. A dedicated section on gonorrhea at the subsequent STI & HIV World Congress (July 9-12, 2017, Rio de Janeiro, Brazil) also focused on antibiotic resistance andways tomitigate the problem, in light of potential threats of super-gonococcal strains untreatable by existing antibiotics. During the Congress, The Lancet Infectious Diseases launched its Commission on STIs, which stated that ultimately, a gonococcal vaccine might be the only sustainable solution for gonorrhea control. Like N. meningitides, N. gonorrhoeae only infects humans, with no known animal or environmental reservoir. Female mice, which are only transiently susceptible to N. gonorrhoeae infection during proestrus, are the most commonly used animal model to study gonococcal pathogenesis and as a challenge model in gonococcal vaccine research. The bacterium possesses multiple virulence factors that help it adhere to and invade host epithelial cells, as well as evade host immune defenses through its highly variable surface antigens. This may explain why repeat infection is very common as the body fails to build an effective adaptive immune response. Upon exposure to N. gonorrhoeae through sexual contact, an estimated 30% of men and 80% of women can become infected, while asymptomatic infection can occur in 10% of infectedmen and 80%of infectedwomen.Many factors are at play, including host vaginalmicrobiota, which can contribute to the differences in gonococcal infectivity and pathogenesis. Knowledge of host immune