Zhu Weiyan, Chen Ching-Ju, Thomas Christopher E, Anderson James E, Jerse Ann E, Sparling P Frederick
Department of Medicine, University of North Carolina Chapel Hill, NC, USA.
Front Microbiol. 2011 Jun 3;2:124. doi: 10.3389/fmicb.2011.00124. eCollection 2011.
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 Here we discuss the state of the field, including our unpublished data regarding efficacy in the mouse model of either viral replicon particle (VRP) vaccines, or outer membrane vesicle (OMV) vaccines.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.
自然感染后对淋球菌的免疫反应通常对再次感染几乎没有免疫力，这是由于淋球菌的抗原变异以及免疫反应的重新定向或抑制。布林顿及其同事证明，用纯化的菌毛疫苗对男性人类志愿者进行肠胃外免疫可对同源菌株的感染提供部分保护。然而，该疫苗在一项临床试验中失败了。最近的疫苗研发工作集中在女性生殖器淋球菌感染的小鼠模型上。在此，我们讨论该领域的现状，包括我们关于病毒复制子颗粒（VRP）疫苗或外膜囊泡（OMV）疫苗在小鼠模型中的疗效的未发表数据。尽管血清和粘膜抗体反应良好，但OMV疫苗仍告失败。由PorB-VRP初免加重组PorB加强免疫组成的方案后的保护作用与明显的Th1反应相关，但与抗体反应无关。保护作用可能归因于VRP载体强大的佐剂效应。包括表达淋球菌感染所需人类基因的新型转基因小鼠在内的新工具应能推动未来的研究。需要免疫替代指标。淋球菌中抗菌耐药性趋势的增加使得疫苗的研发更加紧迫。
