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Published on: November 5, 2019
C-Terminal Clostridium perfringens Enterotoxin-Mediated Antigen Delivery for Nasal Pneumococcal Vaccine
Hidehiko Suzuki1, Akihiro Watari2, Eri Hashimoto3
1Laboratory 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.
Insights
A novel nasal vaccine using a Clostridium perfringens enterotoxin fragment (C-CPE) effectively targets nasopharynx-associated lymphoid tissue (NALT). This system delivers pneumococcal surface protein A (PspA), inducing protective immunity against Streptococcus pneumoniae.
Area of Science:
- Vaccinology
- Immunology
- Microbiology
Background:
- Mucosal vaccines require efficient delivery to tissues like the nasopharynx-associated lymphoid tissue (NALT).
- Claudin-4 targeting via Clostridium perfringens enterotoxin C-terminal fragment (C-CPE) previously showed effective antigen delivery to NALT.
- Pneumococcal surface protein A (PspA) is a key antigen for protection against Streptococcus pneumoniae.
Purpose of the Study:
- To develop a nasal vaccine against pneumococcal infection using the C-CPE delivery system.
- To evaluate the efficacy of a PspA-C-CPE fusion protein for nasal immunization.
Main Methods:
- Fused C-CPE with PspA to create PspA-C-CPE.
- Administered PspA-C-CPE via nasal immunization in a preclinical model.
- Assessed PspA-specific immune responses (IgG and IgA) in serum, nasal wash, and bronchoalveolar lavage fluid (BALF).
- Evaluated protection against pneumococcal challenge.
Main Results:
- PspA-C-CPE efficiently bound to NALT epithelium and M cells via claudin-4.
- Nasal immunization induced PspA-specific IgG in serum and BALF.
- Significant PspA-specific IgA was detected in nasal wash and BALF.
- Induced immune responses provided protection against pneumococcal infection.
Conclusions:
- The C-CPE system is a promising platform for developing effective nasal vaccines.
- Claudin-4 targeting facilitates antigen delivery to NALT for mucosal immunity.
- This approach offers a potential strategy for a pneumococcal nasal 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.
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