title: C-Terminal Clostridium perfringens Enterotoxin-Mediated Antigen Delivery for Nasal Pneumococcal Vaccine.
abstract: Efficient vaccine delivery to mucosal tissues including mucosa-associated lymphoid tissues is essential for the development of mucosal vaccine. We previously reported that claudin-4 was highly expressed on the epithelium of nasopharynx-associated lymphoid tissue (NALT) and thus claudin-4-targeting using C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) effectively delivered fused antigen to NALT and consequently induced antigen-specific immune responses. In this study, we applied the C-CPE-based vaccine delivery system to develop a nasal pneumococcal vaccine. We fused C-CPE with pneumococcal surface protein A (PspA), an important antigen for the induction of protective immunity against Streptococcus pneumoniae infection, (PspA-C-CPE). PspA-C-CPE binds to claudin-4 and thus efficiently attaches to NALT epithelium, including antigen-sampling M cells. Nasal immunization with PspA-C-CPE induced PspA-specific IgG in the serum and bronchoalveolar lavage fluid (BALF) as well as IgA in the nasal wash and BALF. These immune responses were sufficient to protect against pneumococcal infection. These results suggest that C-CPE is an efficient vaccine delivery system for the development of nasal vaccines against pneumococcal infection.
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watari
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hashimoto
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yonemitsu
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.affiliation: Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan; Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D062506:Claudin-4 / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D062506:Claudin-4; D004768:Enterotoxins; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; C035598:enterotoxin, Clostridium; C051592:pneumococcal surface protein A