FIBRONECTIN-BINDING PROTEIN-I OF STREPTOCOCCUS-PYOGENES IS A PROMISING ADJUVANT FOR ANTIGENS DELIVERED BY MUCOSAL ROUTE

A common problem in human vaccinology is the limited availability of e fficient and non-toxic adjuvants capable of promoting mucosal response s. The potential usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as immunological adjuvant was assessed using o valbumin (OVA) as a model antigen. Mice were immunized by intranasal r oute, either with soluble OVA or OVA covalently coupled to Sfbl. Immun ization with OVA-Sfbl resulted in the elicitation of about 100-fold hi gher titers of anti-OVA serum IgG than using OVA alone. The anti-OVA I gG subclass pattern was dominated in both groups of mice by IgG1, foll owed by IgG2b, IgG2a, and IgG3. Immunization with OVA-Sfbl also result ed 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 prolifera tive response to restimulation with soluble OVA in vitro. Phenotypic a nalysis of proliferating cells showed an enrichment in CD4(+) T cells, producing a pattern of cytokines (IL-4, IL-5, IL-6 and IL-10) charact eristic of Th2-type cells. In contrast to immunization with soluble OV A alone, OVA-Sfbl induced the generation of CD8(+) OVA-specific cytoto xic cells. These results demonstrate that Sfbl represents a promising mucosal adjuvant able to substantially improve cellular, humoral and m ucosal responses when coupled to an antigen administered by intranasal route.