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 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.
Medina
E
E
Division of Microbiology, GBF-National Research Centre for Biotechnology, Braunschweig, Germany.
Talay
S R
SR
Chhatwal
G S
GS
Guzmán
C A
CA
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D018928:Immunity, Mucosal; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007132:Immunoglobulin Isotypes; C078635:fibronectin-binding proteins, bacterial; D010047:Ovalbumin