A novel mucosal vaccine targeting Peyer's patch M cells induces protective antigen-specific IgA responses

• Published in: International immunology Vol. 26; no. 11; pp. 619 - 625
• Main Authors: Shima, Hideaki, Watanabe, Takashi, Fukuda, Shinji, Fukuoka, Shin-Ichi, Ohara, Osamu, Ohno, Hiroshi
• Format: Journal Article
• Language: English
• Published: England 01.11.2014
• Subjects: Animals; Antibody Specificity - immunology; Antigens - immunology; Antigens, Bacterial - immunology; GPI-Linked Proteins - genetics; GPI-Linked Proteins - immunology; Immunity, Mucosal; Immunoglobulin A - immunology; Immunoglobulin A, Secretory - immunology; Male; Mice; Mice, Knockout; Mucous Membrane - immunology; Peyer's Patches - immunology; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Salmonella Infections - prevention & control; Salmonella typhimurium - immunology; Vaccines - administration & dosage; Vaccines - immunology; mucosal vaccine; vaccine delivery; IgA; M cell
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxu061

Mucosal vaccines can induce mucosal immunity, including antigen-specific secretory IgA production, to protect from invasion by pathogens and to neutralize toxins at mucosal surfaces. We established an effective antigen-delivering fusion protein, anti-GP2-SA, as a mucosal vaccine. The anti-GP2-SA consists of streptavidin (SA) fused to the antigen-binding fragment region from a mAb against glycoprotein 2 (GP2), an antigen-uptake receptor specifically expressed on M cells. Anti-GP2-SA targets antigen-sampling M cells in the follicle-associated epithelium covering Peyer's patches. Immunofluorescence showed that anti-GP2-SA specifically bound to M cells. Orally administered biotinylated ovalbumin peptide (bOVA) conjugated with anti-GP2-SA more efficiently induced OVA-specific fecal IgA secretion compared with bOVA alone or bOVA conjugated with SA. Furthermore, mice immunized by oral administration of the biotinylated Salmonella enterica serovar Typhimurium (S. Typhimurium) lysate conjugated with anti-GP2-SA were significantly better protected from subsequent infection by virulent S. Typhimurium than mice treated with the bacterial lysate alone or conjugated with SA. These results suggest that anti-GP2-SA-based M-cell-targeting vaccines are a novel strategy for inducing efficient mucosal immunity.