The FAI protein of group C streptococci acts as a mucosal adjuvant by the specific targeting and activation of B cells.
Adjuvants are usually required to stimulate efficient immune responses after vaccination by the mucosal route. Unfortunately, only a few molecules have been described, which exhibit this property. Thus, there is an urgent need to develop new mucosal adjuvants. Our results demonstrate that the fibrinogen-albumin-IgG receptor (FAI) from group C streptococci is a promising mucosal adjuvant. Strong antigen-specific antibody responses were stimulated at both systemic and mucosal levels when model antigens were co-administered with FAI. Immunizations performed using truncated derivatives demonstrated that the fragment encompassing the IgG- and fibrinogen-binding regions represents the minimal domain possessing adjuvant activity. FAI specifically targets B cells, thereby supporting their activation and antibody production, even in the absence of T cell help. Co-administration of antigens with FAI also resulted in elicitation of strong antibody responses in CBA/N Xid mice, which exhibit a deficiency in humoral immunity. The overcoming of their unresponsiveness by co-administration of FAI suggests that this promising adjuvant can be exploited for the establishment of vaccination strategies in patients affected by immune deficiencies of the B cell compartment.
Schulze
Kai
K
Division of Microbiology, Department of Vaccinology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Goldmann
Oliver
O
Medina
Eva
E
Guzmán
Carlos A
CA
D000281:Administration, Intranasal; D000418:Albumins / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005340:Fibrinogen / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013291:Streptococcus / Q000276:immunology*
D000418:Albumins; D000906:Antibodies; D017452:Receptors, IgG; D011994:Recombinant Proteins; D005340:Fibrinogen; D010047:Ovalbumin