Human Experimentation with Neisseria gonorrhoeae: Progress and Goals

Infection with Neisseria gonorrhoeae has adverse consequences for reproductive health and facilitates the transmission of the human immunodeficiency virus. A major limitation in the development of gonococcal vaccines has been the lack of an animal model. Urethral infection can be initiated in male volunteer subjects through urethral inoculation. Several hundred patients have participated in studies using this experimental infection model. These studies have helped define the natural history of experimental infection and provided a better understanding of phenotypic and genotypic variation of gonococci in vivo. Isogenic molecular mutants can be used to define a role for gonococcal surface structures, including pilin and transferrin-binding proteins; recent results demonstrate that gonococci unable to express transferrin- and lactoferrin-binding proteins cannot cause urethral infection. The experimental model has proven to be an efficient means of studying gonococcal infection and focusing vaccine development. In addition, this model should allow vaccines to be tested quickly and efficiently.