Remember me
Research ArticleVaccines
Open Access | 
10.1172/JCI166827
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Kawai, A. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Tokunoh, N. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Kawahara, E. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Tamiya, S. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Okamura, S. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Ono, C.
in:
JCI
|
PubMed
|
Google Scholar
|
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Anindita, J. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Tanaka, H.
in:
JCI
|
PubMed
|
Google Scholar
|
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Akita, H. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Yamasaki, S.
in:
JCI
|
PubMed
|
Google Scholar
|
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Kunisawa, J. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Okamoto, T.
in:
JCI
|
PubMed
|
Google Scholar
|
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by Matsuura, Y. in: JCI | PubMed | Google Scholar
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Hirai, T.
in:
JCI
|
PubMed
|
Google Scholar
|
1Laboratory of Nano-Design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, and
2Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
3The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
4Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
5Center for Infectious Disease Education and Research and
6Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
7Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
8Center for Advanced Modalities and DDS, Osaka University, Osaka, Japan.
9Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
10Laboratory of Molecular Immunology, Immunology Frontier Research Center, and
11Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
12Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
13Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases,
14Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, and
15Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
Address correspondence to: Yasuo Yoshioka, Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81.66.877.4919; Email: y-yoshioka@biken.osaka-u.ac.jp.
Find articles by
Yoshioka, Y.
in:
JCI
|
PubMed
|
Google Scholar
|
Published December 1, 2023 - More info
Published in Volume 133, Issue 23 on December 1, 2023
Related article:
Abstract
Despite the worldwide application of vaccination and other antiviral interventions, pulmonary viral infections remain a persistent threat to human health. The 1918 influenza pandemic killed more than 40 million people in just one year, and the SARS-CoV-2 pandemic has killed more than 6.9 million people since 2019. While the current approved COVID-19 vaccines are administered parenterally and induce systemic immunity, they only prevent the progression to severe disease. Thus, other vaccine platforms are still needed for completely preventing the disease and subsequent transmission. In this issue of the JCI, Kawai et al. present an adjuvant-free subunit (RBD-HA) fusion vaccine, which produces robust IgG and IgA antibody responses against SARS-CoV-2, enriched within the nasal cavity, by using the host’s preexisting immunity to influenza infection. This preclinical study has tremendous implications for future mucosal vaccine design and provides a roadmap for generating a safer and effective intranasal vaccine against pulmonary infections.
Authors
Kim A. Tran, Maziar Divangahi
× AbstractIntranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor-binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV-infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and CD4+ T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines.
Graphical Abstract
Introduction
The SARS-CoV-2 pandemic has accelerated vaccine development at an unprecedented rate. Several types of COVID-19 vaccines, including mRNA and adenovirus-vector vaccines expressing the SARS-CoV-2 spike glycoprotein, provide highly effective protection and have been widely used (1, 2). Currently, approved COVID-19 vaccines are administered intramuscularly, inducing robust systemic immune responses, such as circulating antibodies and CD4+ and CD8+ T cells, and have demonstrated the ability to protect against severe disease and reduce mortality (1–3). Many pathogens, including the SARS-CoV-2 and influenza virus, initiate infections in the upper respiratory tract. However, traditional parenteral vaccines elicit poor mucosal immunity, as evidenced by secretory IgA in the upper respiratory tract (4, 5). Thus, they do not completely prevent viral infections or their transmission (6, 7). Hence, the development of intranasal vaccines capable of inducing IgA on mucosal surfaces as well as IgG in the systemic circulation is desired.
Subunit vaccines, which use pathogen-derived proteins or peptides as vaccine antigens, have several advantages over other vaccine types, such as live-attenuated vaccines and inactivated vaccines (8). These advantages include superior safety, easy upscaling of production, low production costs, and easy storage requirements. However, due to the mucosal barrier that blocks the delivery of antigens to antigen-presenting cells (APCs), such as DCs, macrophages, and B cells, intranasal subunit vaccines are inefficient in inducing an antigen-specific immune response. As a result, while attempts have been made to develop intranasal subunit vaccines used in combination with adjuvants, there are concerns about adverse reactions (9). For example, a human clinical trial of an intranasal influenza vaccine containing an inactivated influenza virus plus an adjuvant was discontinued due to suspicions that the combined use of adjuvant would cause Bell’s palsy in vaccinated individuals in rare cases (10). Therefore, no intranasal subunit vaccine has been approved. Given the problems, an adjuvant-free intranasal subunit vaccine with enhanced antigen delivery would be ideal.
The delivery of antigens to APCs is a key strategy for an effective vaccine (11). In intranasal vaccines, there are two major challenges to delivering antigens to APCs. The first is the mucosal epithelial barrier, which keeps antigens outside the body. Furthermore, even if antigens penetrate the first barrier, they need to be efficiently delivered to APCs and activated to trigger strong antigen-specific immune responses. However, these hurdles do not hold true for antigens against which we already have specific antibodies. Recently, several studies indicated that antibodies, such as IgA, in the nasal cavity aid the passage of bound antigens through the mucosal barrier (12–14). Furthermore, the interaction of the Fc portion of IgG with its receptors (FcγRs) on APCs substantially promotes antigen uptake and activation of APCs (15, 16). Therefore, utilizing preexisting immunity induced by previous infections may be an extremely effective tool for enhancing vaccine effectiveness. For example, influenza virus infection induces not only systemic IgG but also mucosal IgA and IgG to the HA glycoprotein on the influenza virus surface, and many human adults naturally have preexisting antibodies to HA from previous exposure to the seasonal influenza virus (17). Therefore, our study focused on the idea that a vaccine antigen fused with a carrier protein that recognizes preexisting antibodies could facilitate passage through the mucosal barrier and be picked up by APCs simultaneously.
Here, we made RBD-HA, a fusion of the receptor-binding domain (RBD) of the spike protein derived from SARS-CoV-2 as a vaccine target with HA, to test whether HA-specific preexisting immunity could be utilized. We showed that intranasal immunization of previously influenza virus–infected mice with RBD-HA without an adjuvant elicited a robust production of RBD-specific systemic IgG and mucosal IgA by utilizing HA-specific preexisting IgG and CD4+ T cells. Furthermore, RBD-HA protected mice in both the upper and lower respiratory tracts against SARS-CoV-2 infection. In addition, preexisting immunity induced by Streptococcus pneumoniae infection and an injectable mRNA vaccine can be utilized, suggesting high versatility of the vaccine system. Thus, we propose an adjuvant-free intranasal vaccine platform that could induce strong systemic and mucosal protective immunity.
ResultsIntranasal vaccine with unadjuvanted RBD-HA induces antigen-specific systemic IgG and mucosal IgA. Many studies have used large volumes (i.e., 20 to 30 μL/mouse) of vaccine-containing solutions as nasal vaccines in mouse models to immunize the upper respiratory and lower respiratory tracts, including the lungs; however, this approach might not accurately reflect nasal vaccine outcomes in humans. Previous studies have revealed that intranasal administration of a fluid volume less than 10 μL can limit antigen delivery to the upper respiratory tract of mice (
Comments (0)