Medina E, Talay S R, Chhatwal G S, Guzmán C A
Division of Microbiology, GBF-National Research Centre for Biotechnology, Braunschweig, Germany.
Eur J Immunol. 1998 Mar;28(3):1069-77. doi: 10.1002/(SICI)1521-4141(199803)28:03<1069::AID-IMMU1069>3.0.CO;2-P.
A common problem in human vaccinology is the limited availability of efficient and non-toxic adjuvants capable of promoting mucosal responses. The potential usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as immunological adjuvant was assessed using ovalbumin (OVA) as a model antigen. Mice were immunized by intranasal route, either with soluble OVA or OVA covalently coupled to Sfbl. Immunization with OVA-Sfbl resulted in the elicitation of about 100-fold higher titers of anti-OVA serum IgG than using OVA alone. The anti-OVA IgG subclass pattern was dominated in both groups of mice by IgG1, followed by IgG2b, IgG2a, and IgG3. Immunization with OVA-Sfbl also resulted in the elicitation of OVA-specific IgA in lung washes (24% of the total IgA), which was absent in mice immunized with OVA alone. Spleen cells from OVA-Sfbl-immunized mice also gave a much stronger proliferative response to restimulation with soluble OVA in vitro. Phenotypic analysis of proliferating cells showed an enrichment in CD4+ T cells, producing a pattern of cytokines (IL-4, IL-5, IL-6 and IL-10) characteristic of Th2-type cells. In contrast to immunization with soluble OVA alone, OVA-Sfbl induced the generation of CD8+ OVA-specific cytotoxic cells. These results demonstrate that Sfbl represents a promising mucosal adjuvant able to substantially improve cellular, humoral and mucosal responses when coupled to an antigen administered by intranasal route.
人类疫苗学中的一个常见问题是,能够促进黏膜反应的高效且无毒佐剂的可用性有限。使用卵清蛋白(OVA)作为模型抗原,评估了化脓性链球菌的纤连蛋白结合蛋白I(Sfbl)作为免疫佐剂的潜在效用。小鼠通过鼻内途径免疫,使用可溶性OVA或与Sfbl共价偶联的OVA。与单独使用OVA相比,用OVA-Sfbl免疫产生的抗OVA血清IgG滴度高出约100倍。两组小鼠的抗OVA IgG亚类模式均以IgG1为主,其次是IgG2b、IgG2a和IgG3。用OVA-Sfbl免疫还导致肺灌洗液中产生OVA特异性IgA(占总IgA的24%),而单独用OVA免疫的小鼠中则没有。来自OVA-Sfbl免疫小鼠的脾细胞在体外对可溶性OVA再刺激也产生了更强的增殖反应。对增殖细胞的表型分析显示CD4+ T细胞富集,产生Th2型细胞特有的细胞因子模式(IL-4、IL-5、IL-6和IL-10)。与单独用可溶性OVA免疫不同,OVA-Sfbl诱导产生了CD8+ OVA特异性细胞毒性细胞。这些结果表明,Sfbl是一种有前景的黏膜佐剂,当与通过鼻内途径给药的抗原偶联时,能够显著改善细胞、体液和黏膜反应。