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首页> 外文期刊>Clinical and vaccine immunology: CVI >Induction of Cross-Serovar Protection against Genital Chlamydial Infection by a Targeted Multisubunit Vaccination Approach
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Induction of Cross-Serovar Protection against Genital Chlamydial Infection by a Targeted Multisubunit Vaccination Approach

机译：有针对性的多亚基疫苗接种方法诱导针对生殖器衣原体感染的跨血清保护。

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An important consideration for antichlamydial vaccine development is the induction of cross-serovar protection, since multiple serovars (D to L) of Chlamydia trachomatis cause genital infections. We have shown previously that vaccination with C. trachomatis-derived recombinant chlamydial protease-like activity factor (rCPAF) induced significant earlier resolution of Chlamydia muridarum infection and reduced oviduct pathology. However, the vaccinated mice continued to shed chlamydiae for up to 2 weeks after challenge. In this study, C. trachomatis serovar D recombinant proteins, such as recombinant major outer membrane protein (rMOMP), recombinant inclusion membrane protein A (rIncA), and rCPAF were administered intranasally, individually or in combinations, with murine interleukin-12 (IL-12) as an adjuvant, and cross-species immunity against intravaginal C. muridarum infection was examined. Immunization with rCPAF plus IL-12 (rCPAF+IL-12), compared to immunization with rIncA+IL-12 or rMOMP+IL-12, induced the greatest antigen-specific gamma interferon production from purified CD4+ T cells and concurrently enhanced serum antibody production. All (100%) the animals vaccinated with rCPAF+IL-12 alone or in any combination completely resolved the infection by day 18 after challenge compared to animals vaccinated with rIncA+IL-12 (50%), rMOMP+IL-12 (33%), or phosphate-buffered saline (mock vaccinated; 0%). Moreover, oviduct pathology in mice vaccinated by any regimen that included rCPAF, but not rMOMP+IL-12 or rIncA+IL-12 alone, was markedly reduced compared to mock-immunized animals. The addition of rMOMP and/or rIncA did not significantly enhance the rCPAF+IL-12-induced effect on bacterial clearance or oviduct pathology. These results suggest a greater conservation of protective linear antigenic epitopes within CPAF than MOMP or IncA across the examined serovars and the need to identify other highly conserved antigens for use with rCPAF in a multisubunit recombinant vaccine.
机译：抗沙眼衣原体疫苗开发的重要考虑因素是诱导交叉血清保护，因为沙眼衣原体的多种血清（D至L）会导致生殖器感染。先前我们已经证明了用 C进行疫苗接种。沙眼衣原体来源的重组衣原体蛋白酶样活性因子（rCPAF）可以显着地早期解决muridarum衣原体感染并降低输卵管病理。但是，接种疫苗的小鼠在攻击后长达2周继续脱落衣原体。在本研究中， C。沙眼衣原体D重组蛋白，例如重组主要外膜蛋白（rMOMP），重组包涵体膜蛋白A（rIncA）和rCPAF与鼠白细胞介素12（IL-12）鼻内，单独或组合给药）作为佐剂，并且具有针对阴道内 C的种间免疫性。检查了muridarum 感染。与使用rIncA + IL-12或rMOMP + IL-12进行免疫相比，使用rCPAF加IL-12（rCPAF + IL-12）进行免疫可诱导纯化CD4 + T细胞并同时增强血清抗体的产生。与接种rIncA + IL-12（50％），rMOMP + IL-12的动物相比，所有（100％）单独接种rCPAF + IL-12或以任何组合形式接种rCPAF + IL-12的动物在攻击后第18天完全可以消除感染。 ％）或磷酸盐缓冲液（模拟疫苗; 0％）。此外，与模拟免疫的动物相比，用任何包括rCPAF而不是单独的rMOMP + IL-12或rIncA + IL-12的疫苗接种的小鼠输卵管病理显着降低。 rMOMP和/或rIncA的添加并未显着增强rCPAF + IL-12诱导的对细菌清除或输卵管病理的影响。这些结果表明，在被检查的血清中，CPAF中的保护性线性抗原表位比MOMP或IncA的保留程度更高，并且需要鉴定与rCPAF一起用于多亚基重组疫苗的其他高度保守的抗原。

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