Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia
IntroductionRespiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during...
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| Format: | Article |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282016/full |
| _version_ | 1797386044137537536 |
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| author | Eigo Kawahara Eigo Kawahara Takehiko Shibata Toshiro Hirai Toshiro Hirai Toshiro Hirai Toshiro Hirai Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka |
| author_facet | Eigo Kawahara Eigo Kawahara Takehiko Shibata Toshiro Hirai Toshiro Hirai Toshiro Hirai Toshiro Hirai Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka |
| author_sort | Eigo Kawahara |
| collection | DOAJ |
| description | IntroductionRespiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.MethodsMice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Escherichia coli (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.ResultsmG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.DiscussionThese results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines. |
| first_indexed | 2024-03-08T22:04:09Z |
| format | Article |
| id | doaj.art-5393c2eafe5a423a9bf6fd3b5b7d1638 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T22:04:09Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5393c2eafe5a423a9bf6fd3b5b7d16382023-12-19T10:32:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12820161282016Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophiliaEigo Kawahara0Eigo Kawahara1Takehiko Shibata2Toshiro Hirai3Toshiro Hirai4Toshiro Hirai5Toshiro Hirai6Yasuo Yoshioka7Yasuo Yoshioka8Yasuo Yoshioka9Yasuo Yoshioka10Yasuo Yoshioka11Yasuo Yoshioka12Yasuo Yoshioka13Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanVaccine Creation Group, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Microbiology, Tokyo Medical University, Tokyo, JapanLaboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanVaccine Creation Group, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanInstitute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, JapanCenter for Advanced Modalities and DDS, Osaka University, Osaka, JapanLaboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanVaccine Creation Group, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanInstitute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, JapanCenter for Advanced Modalities and DDS, Osaka University, Osaka, JapanInnovative Vaccine Research and Development Center, The Research Foundation for Microbial Diseases of Osaka University, Osaka, JapanGlobal Center for Medical Engineering and Informatics, Osaka University, Osaka, JapanCenter for Infectious Disease Education and Research, Osaka University, Osaka, JapanIntroductionRespiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.MethodsMice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Escherichia coli (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.ResultsmG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.DiscussionThese results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282016/fulladjuvantCpG oligodeoxynucleotideeosinophilG proteinrespiratory syncytial virusvaccine |
| spellingShingle | Eigo Kawahara Eigo Kawahara Takehiko Shibata Toshiro Hirai Toshiro Hirai Toshiro Hirai Toshiro Hirai Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Yasuo Yoshioka Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia Frontiers in Immunology adjuvant CpG oligodeoxynucleotide eosinophil G protein respiratory syncytial virus vaccine |
| title | Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| title_full | Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| title_fullStr | Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| title_full_unstemmed | Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| title_short | Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| title_sort | non glycosylated g protein with cpg odn provides robust protection against respiratory syncytial virus without inducing eosinophilia |
| topic | adjuvant CpG oligodeoxynucleotide eosinophil G protein respiratory syncytial virus vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1282016/full |
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