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Abstract

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 (SfbI) 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 SfbI. Immunization with OVA-SfbI resulted in the elicitation of about 100-fold higher titres 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-SfbI 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-SfbI immunized mice also gave a much stronger proliferative response to in vitro restimulation with soluble OVA. 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-SfbI induced the generation of CD8+ OVA-specific cytotoxic cells. These results demonstrate that SfbI represents a promising mucosal adjuvant able to substantially improve cellular, humoral and mucosal responses, when coupled to an antigen administered by intranasal route.

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