Chlamydia trachomatis urogenital tract infection causes pelvic inflammatory disease and infertility, increases the risk of co-infection with HPV and HIV. Chlamydial vaccination is considered the most promising approach to prevent and control its infection. Among various chlamydial vaccine candidates, chlamydial protease-like activity factor (CPAF) have been reported to provide robust protective immunity against genital chlamydial infection in mice with reduced vaginal shedding and oviduct pathology. However, CPAF is a serine protease which has enzymatical activity to degrade a large number of substrates. In order to increase the safety of CPAF vaccine, in this study, we used a mutant CPAF that is deficient in enzymatical activity to determine whether proteolytic activity of CPAF affect its vaccine efficacy. The wild type or mutant CPAF immunization causes a significant lower chlamydial shedding from the vaginal and resolve the infection as early as day 20, compared to day 28 in adjuvant control mice. More important, reduced upper reproductive tract pathology were also observed in these two groups. The mutant or wild type CPAF immunization induced not only robust splenic IFN-γ and serum IgG2a but also sIgA secretion in the vaginal fluids. Furthermore, neutralization of chlamydia with immune sera did not provide protection against oviduct pathology. However, adoptive transfer of CD4⁺ splenocytes isolated from the mutant or wild type CPAF immunized mice resulted in a significant and comparable reduced oviduct pathology. Our results indicate mutant CPAF vaccination is as same efficacy as wild type, and the protection relies on CD4⁺ T cells, which will further promote the development of CPAF as clinical chlamydial vaccine.

沙眼衣原体泌尿生殖道感染会导致盆腔炎和不孕症，增加同时感染 HPV 和 HIV 的风险。衣原体疫苗接种被认为是预防和控制其感染的最有希望的方法。在各种衣原体候选疫苗中，据报道衣原体蛋白酶样活性因子 (CPAF) 可在阴道脱落和输卵管病理减少的小鼠中提供针对生殖器衣原体感染的强大保护性免疫。然而，CPAF是一种丝氨酸蛋白酶，具有降解大量底物的酶活性。为了提高CPAF疫苗的安全性，在本研究中，我们使用酶活性缺陷的突变CPAF来确定CPAF的蛋白水解活性是否影响其疫苗效力。与佐剂对照小鼠的第 28 天相比，野生型或突变体 CPAF 免疫导致阴道衣原体脱落显着减少，并在第 20 天解决感染。更重要的是，在这两组中还观察到上生殖道病理减少。突变型或野生型 CPAF 免疫不仅诱导了强大的脾脏 IFN-γ 和血清 IgG2a，而且还诱导了阴道液中的 sIgA 分泌。此外，中和带有免疫血清的衣原体不能提供针对输卵管病理学的保护。然而，从突变型或野生型 CPAF 免疫小鼠中分离出的 CD4 ⁺脾细胞的过继转移导致显着且相当的输卵管病理学减少。我们的结果表明突变CPAF疫苗与野生型具有相同的功效，并且保护依赖于CD4 ⁺ T细胞，这将进一步促进CPAF作为临床衣原体疫苗的发展。