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Immunobiology of the Tomatine adjuvant

机译：番茄佐剂的免疫生物学

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Soluble or sub-unit protein vaccines alone are incapable of generating antigen-specific cellular immune responses. This failure can be attributed to the manner in which the immune system processes antigen; endogenous antigens are cycled through the MHC class I pathway to stimulate CD8(+) restricted responses and exogenous antigens are processed through the MHC class 11 pathway to generate humoral immunity. Traditionally sub-unit vaccines have been formulated with adjuvants to enhance immunogenicity, however in the last decade a number of adjuvants have been developed that effectively stimulate the generation of both humoral and cellular immune responses, although the manner in which they exert their effects has not been investigated. Here we describe Tomatine, a glycoalkaloid based adjuvant, capable of stimulating potent antigen-specific humoral and cellular immune responses that contribute to protection against malaria, Francisella tularensis and regression of experimental tumors. Using in vivo models we investigated the manner in which cellular immune responses were generated by Tomatine. We established that Tomatine did not require either lymph node or splenic macrophages to generate cytotoxic T lymphocytes (CTL) and delivered soluble protein into a pathway not dependant on the machinery of the classical MHC class I pathway. We also observed that at the molecular level Tomatine required both CD80 and CD86 costimulation to engender antigen-specific cellular immunity.
机译：单独的可溶性或亚单位蛋白疫苗无法产生抗原特异性细胞免疫应答。这种失败可以归因于免疫系统处理抗原的方式。内源性抗原通过MHC I类途径循环以刺激CD8（+）限制性反应，外源性抗原通过MHC 11类途径进行加工以产生体液免疫。传统上，亚单位疫苗已与佐剂一起配制以增强免疫原性，但是在最近十年中，已开发出许多佐剂，可有效刺激体液和细胞免疫反应的产生，尽管它们发挥作用的方式尚未被调查。在这里，我们描述了番茄素，一种基于生物碱的佐剂，能够刺激有效的抗原特异性体液和细胞免疫应答，从而有助于抵抗疟疾，弗朗西斯菌和实验性肿瘤的消退。使用体内模型，我们研究了番茄素产生细胞免疫应答的方式。我们建立了番茄素不需要淋巴结或脾巨噬细胞来产生细胞毒性T淋巴细胞（CTL）并将可溶性蛋白递送到不依赖于经典MHC I类途径的途径的途径。我们还观察到，在分子水平上，番茄素需要CD80和CD86共刺激才能产生抗原特异性细胞免疫。

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