Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci

Chieko Yokota; Kosuke Fujimoto; Natsuko Yamakawa; Masamitsu Kono; Daichi Miyaoka; Masaki Shimohigoshi; Miho Uematsu; Miki Watanabe; Yukari Kamei; Akira Sugimoto; Natsuko Kawasaki; Takato Yabuno; Tomotaka Okamura; Eisuke Kuroda; Shigeto Hamaguchi; Shintaro Sato; Muneki Hotomi; Yukihiro Akeda; Ken J Ishii; Yasuhiro Yasutomi; Kishiko Sunami; Satoshi Uematsu

doi:10.1186/s41232-023-00305-2

Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci

Inflamm Regen. 2023 Nov 15;43(1):55. doi: 10.1186/s41232-023-00305-2.

Authors

Chieko Yokota^#^{1

2}, Kosuke Fujimoto^#^{1

3}, Natsuko Yamakawa⁴, Masamitsu Kono⁵, Daichi Miyaoka¹, Masaki Shimohigoshi¹, Miho Uematsu¹, Miki Watanabe¹, Yukari Kamei^{1

2}, Akira Sugimoto¹, Natsuko Kawasaki¹, Takato Yabuno¹, Tomotaka Okamura⁴, Eisuke Kuroda^{6

7}, Shigeto Hamaguchi^{6

7}, Shintaro Sato^{1

8}, Muneki Hotomi⁵, Yukihiro Akeda⁹, Ken J Ishii¹⁰, Yasuhiro Yasutomi⁴, Kishiko Sunami², Satoshi Uematsu^{11

12

13

14}

Affiliations

¹ Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
² Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
³ Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁴ Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
⁵ Department of Otorhinolaryngology-Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan.
⁶ Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁷ Division of Fostering Required Medica Human Resources, Center for Infectious Diseases Education and Research (CiDER), Osaka University, Osaka, Japan.
⁸ Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
⁹ Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
¹⁰ Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹¹ Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan. uematsu.satoshi@omu.ac.jp.
¹² Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. uematsu.satoshi@omu.ac.jp.
¹³ Research Institute for Drug Discovery Science, Osaka Metropolitan University, Osaka, Japan. uematsu.satoshi@omu.ac.jp.
¹⁴ International Research Center for Infectious Diseases, Osaka Metropolitan University, Osaka, Japan. uematsu.satoshi@omu.ac.jp.

^# Contributed equally.

Abstract

Background: Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques.

Methods: C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia.

Results: Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection.

Conclusions: Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.

Keywords: IgA; Mucosal vaccine; Pneumococcal surface protein A; Streptococcus pneumoniae.

Abstract

Grants and funding