Mechanisms and protective efficacy of nanovaccines against Chlamydia trachomatis

描述（由申请人提供）：沙眼衣原体是一种引起公共卫生关注的性传播细菌，因为它会导致发病率和社会经济负担，如不孕症、异位妊娠和慢性腹痛。尽管多年的疫苗开发努力，没有针对C。沙眼，这可能部分源于无效的输送系统或制剂，这些系统或制剂不能增强免疫反应以实现持久的保护性免疫。因此，有必要探索其他可能有效提高疫苗效力的递送系统。可生物降解的纳米颗粒作为佐剂和递送系统提供了有吸引力的替代方案，因为它们通过向免疫系统提供抗原的受控和持续释放而有效地增强免疫原性。我们开发了两个新的C。沙眼衣原体纳米疫苗，其分别采用PLGA（聚D，L-乳酸-共-乙醇酸）和PLA-PEG（聚D，L-乳酸-聚乙二醇）作为其重组主要外膜蛋白（rMOMP）和肽衍生物（命名为M278）的递送系统。命名的PLGA-rMOMP和PLA-PEG-M278纳米疫苗具有免疫原性、免疫增强性，并触发了深刻的C.沙眼衣原体相关的Th 1保护性免疫应答。我们的目标是研究纳米疫苗与抗原呈递细胞相互作用以激活T细胞的分子机制; Th 1相关保护性免疫应答的T和B细胞介导的效应物，以及免疫相关物是否可以提供针对C的完全保护性免疫。沙眼衣原体感染的小鼠。为了实现我们的目标，提出了两个具体目标。在SA 1中，我们将评估纳米疫苗与抗原呈递细胞的相互作用，以进行受体介导的识别、细胞摄取、加工和T细胞亚群活化，从而产生Th 1保护性免疫应答。在SA 2中，我们将用纳米疫苗免疫小鼠，以测量Th 1细胞和体液保护性免疫相关性，并评估这些相关性是否可以提供针对C的短期和长期保护性免疫。沙眼衣原体感染的小鼠。实现这一提议的目标将对C.沙眼疫苗的研究和改进我们的努力，以开发一种抗衣原体疫苗。

DESCRIPTION (provided by applicant): Chlamydia trachomatis is a sexually transmitted bacterium of public health concerns because it causes morbidity and socioeconomic burdens, such as infertility, ectopic pregnancy and chronic abdominal pain. Despite many years of vaccine development efforts, there is no vaccine against C. trachomatis, which probably stems in part from ineffective delivery systems or formulations that do not bolster immune responses to achieve long-lasting protective immunity. Therefore it is essential to explore other delivery systems that may effectively enhance the vaccine efficacy. Biodegradable nanoparticles offer attractive alternatives as adjuvants and delivery systems because they effectively enhance immunogenicity by providing controlled and sustained release of antigens to the immune system. We have developed two novel C. trachomatis nanovaccines employing PLGA (Poly D, L-lactic-co-glycolic acid) and PLA-PEG (Poly D, L-lactic acid-Polyethylene glycol), respectively as delivery systems for its recombinant major outer membrane protein (rMOMP) and peptide derivative (named M278). The named PLGA-rMOMP and PLA-PEG-M278 nanovaccines were immunogenic, immune-potentiating, and triggered profound C. trachomatis correlative Th1 protective immune responses in mice. Our goals are to investigate the molecular mechanisms by which nanovaccines interact with antigen presenting cells for T cell activation; the T and B cell-mediated effectors of the Th1 correlative protective immune responses, and whether the immune correlates can provide complete protective immunity against C. trachomatis infection in mice. Two specific aims are proposed to accomplish our goals. In SA1 we will assess the interaction of nanovaccines with antigen presenting cells for receptor-mediated recognition, cellular uptake, processing, and T cell subsets activation to produce Th1 protective immune responses. In SA2, we will immunize mice with nanovaccines to measure Th1 cellular and humoral protective immune correlates and evaluate whether these correlates can provide short- and long-term protective immunity against C. trachomatis infection in mice. Achieving this proposal's goals would positively impact C. trachomatis vaccine research and improve our efforts toward developing an anti-Chlamydia vaccine.