Conjugation of protein antigen to microparticulate β-glucan from Saccharomyces cerevisiae:: a new adjuvant for intradermal and oral immunizations
Conjugation of protein antigen to microparticulate β-glucan from Saccharomyces cerevisiae:: a new adjuvant for intradermal and oral immunizations
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DOI：
10.1007/s00253-008-1618-8
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发表时间：
2008-10-01
影响因子：
5
通讯作者：
Hunter, Kenneth W., Jr.
中科院分区：
文献类型：
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作者：
Berner, Vanessa K.;Sura, Michael E.;Hunter, Kenneth W., Jr.
被称为-葡聚糖的免疫刺激葡萄糖聚合物已被研究多年。本实验室从出芽酵母酿酒酵母（Saccharomyces cerevisiae）中制备并表征了一种新型微颗粒β -葡聚糖（MG）。由于MG颗粒被小鼠腹膜巨噬细胞快速吞噬并诱导B7共刺激分子的表达，我们假设MG可以作为疫苗佐剂增强特异性免疫反应。在这里，我们描述了一种通过水溶性碳二亚胺连接将试验疫苗抗原牛血清白蛋白（BSA）偶联到MG的过程。制备了高达0.4 mg BSA/mg mg的偶联物。MG/BSA偶联物仍能被小鼠腹腔巨噬细胞积极吞噬。当通过皮内途径免疫小鼠时，这些偶联物以与原型完全弗氏佐剂相当的方式增强了对BSA的一抗IgG抗体反应。虽然口服MG/BSA初级免疫未引起血清抗BSA抗体滴度的增加，但加强免疫引起了显著的抗BSA抗体反应。这些结果表明，蛋白抗原可以通过碳二亚胺键偶联到MG上，这些偶联物为刺激抗体对蛋白抗原的反应提供了辅助作用。
Immunostimulatory glucose polymers known as beta-glucans have been studied for many years. Our laboratory has prepared and characterized a novel microparticulate beta-glucan (MG) from the budding yeast Saccharomyces cerevisiae. Because MG particles are rapidly phagocytized by murine peritoneal macrophages and induce the expression of B7 costimulatory molecules, we hypothesized that MG could serve as a vaccine adjuvant to enhance specific immune responses. Here, we describe a procedure for conjugating the test vaccine antigen bovine serum albumin (BSA) to MG via water-soluble carbodiimide linkage. Conjugates with up to 0.4 mg of BSA/mg MG were prepared. MG/BSA conjugates were still actively phagocytized by mouse peritoneal macrophages. When used to immunize mice by the intradermal route, these conjugates enhanced the primary IgG antibody response to BSA in a manner comparable to the prototypic complete Freund's adjuvant. Although primary oral immunization with MG/BSA caused no increase in serum anti-BSA antibody titers, booster immunization elicited a significant anti-BSA antibody response. These results suggest that protein antigens can be conjugated to MG via a carbodiimide linkage and that these conjugates provide an adjuvant effect for stimulating the antibody response to the protein antigens.