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.
Highlights
Because various pathogens infect through mucosal tissues, the induction of protective immunity at mucosal tissues is a primary strategy to prevent infectious diseases
To investigate whether a C-terminal fragment of Clostridium perfringens enterotoxin (C-Clostridium perfringens (CPE)) based claudin-4-targeting vaccine delivery system can be used as a nasal pneumococcal vaccine, we genetically fused pneumococcal surface protein A (PspA) with C-CPE (PspA-C-CPE)
We previously found that C-terminus of C-CPE is an activite portion to interacti with claudin-4 [27]
Summary
Because various pathogens infect through mucosal tissues, the induction of protective immunity at mucosal tissues is a primary strategy to prevent infectious diseases. Injection-based immunization induces systemic immune responses but not mucosal. Research for Evolutional Science and Technology (CREST; to H.K.); Kowa Life Science Foundation K.); and Mochida Memorial Foundation for Medical and Pharmaceutical Research (J.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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