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首页> 外文期刊>Infection and immunity >Induction of Protective Immunity against Chlamydia trachomatis Genital Infection by a Vaccine Based on Major Outer Membrane Protein–Lipophilic Immune Response-Stimulating Complexes
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Induction of Protective Immunity against Chlamydia trachomatis Genital Infection by a Vaccine Based on Major Outer Membrane Protein–Lipophilic Immune Response-Stimulating Complexes

机译：基于主要外膜蛋白-亲脂性免疫反应刺激复合物的疫苗诱导的针对沙眼衣原体生殖器感染的保护性免疫

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The significance of delivery systems in modern vaccine design strategies is underscored by the fact that a promising vaccine formulation may fail in vivo due to an inappropriate delivery method. We evaluated the immunogenicity and efficacy of a candidate vaccine comprising the major outer membrane protein (MOMP) of Chlamydia trachomatis delivered with the lipophilic immune response-stimulating complexes (ISCOMs) as a vehicle with adjuvant properties, in a murine model of chlamydial genital infection. Immunocompetent BALB/c mice were immunized intranasally (IN) or intramuscularly (IM) with MOMP, MOMP-ISCOMs, and live or heat-inactivated C. trachomatis serovar D. The level of local genital mucosal Th1 response was measured by assaying for antigen-specific Th1 cell induction and recruitment into the genital mucosa at different times after immunization. Immunization with MOMP-ISCOMs by the IM route induced the greatest and fastest local genital mucosal Th1 response, first detectable 2 weeks after exposure. Among the other routes and regimens tested, only IN immunization with MOMP-ISCOMs induced detectable and statistically significant levels of local genital mucosal Th1 response during the 8-week test period (P < 0.001). In addition, when T cells from immunized mice were adoptively transferred into syngeneic naive animals and challenged intravaginally with Chlamydia, recipients of IM immunization of MOMP-ISCOMs cleared their infection within 1 week and were resistant to reinfection. Animals that received IN immunization of MOMP-ISCOMs were partially protected, shedding fewer chlamydiae than did control mice. Altogether, the results suggested that IM delivery of MOMP-ISCOMs may be a suitable vaccine regimen potentially capable of inducing protective mucosal immunity against C. trachomatisinfection.
机译：由于有希望的疫苗制剂可能由于不适当的递送方法而在体内失败，因此强调了递送系统在现代疫苗设计策略中的重要性。我们评估了包含沙眼衣原体主要外膜蛋白（MOMP）的候选疫苗的免疫原性和功效，该沙眼衣原体与亲脂性免疫应答刺激复合物（ISCOM）一起作为具有佐剂特性的载体，衣原体生殖器感染的小鼠模型。用MOMP，MOMP-ISCOM和活或热灭活的 C鼻内（IN）或肌内（IM）对免疫活性BALB / c小鼠进行免疫。通过检测抗原特异性Th1细胞的诱导和免疫后不同时间募集到生殖器粘膜中来测量局部生殖器粘膜Th1反应水平。通过IM途径用MOMP-ISCOM免疫可诱导最大和最快的局部生殖器粘膜Th1反应，这是在暴露后2周首次检测到的。在测试的其他途径和方案中，只有用MOMP-ISCOM进行的IN免疫可以在8周的测试期间内诱导出可检测的和统计学上显着水平的局部生殖器粘膜Th1反应（ P <0.001）。此外，当将来自免疫小鼠的T细胞过继转移到同系幼稚动物中并用衣原体进行阴道内攻击时，IMMP-ISCOM的IM免疫接受者在1周内清除了感染，并且对再感染具有抵抗力。对MOMP-ISCOM进行IN免疫的动物受到了部分保护，与对照小鼠相比，衣原体减少了。总而言之，结果表明IMMP-ISCOM的IM递送可能是潜在的能够诱导针对 C的保护性粘膜免疫的合适疫苗方案。沙眼菌感染。

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