Abstract
Immune responses to the gonococcus after natural infection ordinarily result in little immunity to reinfection, due to antigenic variation of the gonococcus, and redirection or suppression of immune responses. Brinton and colleagues demonstrated that parenteral immunization of male human volunteers with a purified pilus vaccine gave partial protection against infection by the homologous strain. However, the vaccine failed in a clinical trial. Recent vaccine development efforts have focused on the female mouse model of genital gonococcal infection. Here we discuss the state of the field, including our unpublished data regarding efficacy in the mouse model of either viral replicon particle (VRP) vaccines, or outer membrane vesicle (OMV) vaccines. The OMV vaccines failed, despite excellent serum and mucosal antibody responses. Protection after a regimen consisting of a PorB-VRP prime plus recombinant PorB boost was correlated with apparent Th1, but not with antibody, responses. Protection probably was due to powerful adjuvant effects of the VRP vector. New tools including novel transgenic mice expressing human genes required for gonococcal infection should enable future research. Surrogates for immunity are needed. Increasing antimicrobial resistance trends among gonococci makes development of a vaccine more urgent.
Highlights
NEED FOR A VACCINE FOR GONORRHEA Neisseria gonorrhoeae remains an important disease
Current U.S gonorrhea treatment guidelines increased the dose of parenteral ceftriaxone from 125 to 250 mg to attempt to counteract the slow increases in cephalosporin resistance (Centers for Disease Control, 2010)
We concluded that anti-Rmp blocking antibodies were not responsible for the lack of effectiveness of outer membrane vesicle (OMV) vaccine antigens in vivo
Summary
NEED FOR A VACCINE FOR GONORRHEA Neisseria gonorrhoeae (the gonococcus, or GC) remains an important disease. Calculations of attributable risk show that GC is one of the significant cofactors for HIV transmission (Fleming and Wasserheit, 1999), increasing risks of HIV transmission and acquisition about threefold These factors alone should promote interest in a vaccine for this ancient disease. Another reason to urge development of a gonococcal vaccine is emergence of antibiotic resistant GC. A PubMed search on 12.27/2010 under “gonococcal vaccine” yielded 247 entries, whereas a similar search under “meningococcal vaccine” yielded 3326 entries The reasons for this glaring discrepancy are not obvious, but may include such commercial factors as estimated market size for vaccines, the probability that the public would accept and utilize the vaccine, and who would pay for the vaccine.
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