Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination
Abstract Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01073-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850026172803448832 |
|---|---|
| author | Mizuki Fujisawa Taishi Onodera Daisuke Kuroda Chidchamai Kewcharoenwong Michihito Sasaki Yukari Itakura Kohei Yumoto Arnone Nithichanon Naoto Ito Shinji Takeoka Tadaki Suzuki Hirofumi Sawa Ganjana Lertmemongkolchai Yoshimasa Takahashi |
| author_facet | Mizuki Fujisawa Taishi Onodera Daisuke Kuroda Chidchamai Kewcharoenwong Michihito Sasaki Yukari Itakura Kohei Yumoto Arnone Nithichanon Naoto Ito Shinji Takeoka Tadaki Suzuki Hirofumi Sawa Ganjana Lertmemongkolchai Yoshimasa Takahashi |
| author_sort | Mizuki Fujisawa |
| collection | DOAJ |
| description | Abstract Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated the neutralizing activity of recalled antibodies, primarily targeting an immunodominant site III epitope with hydrophilic and rugged structures. Strikingly, the majority of site III-directed antibodies in the recall response used a convergent VH gene (IGHV3-30), and they exhibited more hydrophilic and shorter paratopes than non-site III antibodies, providing physicochemical advantages for binding to site III. Additionally, several amino acids on heavy chain CDR3 were identified as key sites for acquiring an ultrapotent neutralizing activity through site III binding. Our in-depth analysis of antibody repertoires revealed the molecular signatures of neutralizing antibodies generated by repeated rabies vaccination, possibly as a result of adaptive convergence. |
| format | Article |
| id | doaj-art-b5fcaec3b39f4fb485b9dccc55ecabbc |
| institution | DOAJ |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-b5fcaec3b39f4fb485b9dccc55ecabbc2025-08-20T03:00:37ZengNature Portfolionpj Vaccines2059-01052025-02-0110111410.1038/s41541-025-01073-5Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccinationMizuki Fujisawa0Taishi Onodera1Daisuke Kuroda2Chidchamai Kewcharoenwong3Michihito Sasaki4Yukari Itakura5Kohei Yumoto6Arnone Nithichanon7Naoto Ito8Shinji Takeoka9Tadaki Suzuki10Hirofumi Sawa11Ganjana Lertmemongkolchai12Yoshimasa Takahashi13Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns)Research Center for Drug and Vaccine Development, National Institute of Infectious DiseasesResearch Center for Drug and Vaccine Development, National Institute of Infectious DiseasesDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityDivision of Molecular Pathobiology, International Institute for Zoonosis Control (IIZC), Hokkaido UniversityInstitute for Vaccine Research and Development, Hokkaido UniversityResearch Center for Drug and Vaccine Development, National Institute of Infectious DiseasesDepartment of Microbiology, Faculty of Medicine, Khon Kaen UniversityLaboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu UniversityDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns)Department of Pathology, National Institute of Infectious DiseasesInstitute for Vaccine Research and Development, Hokkaido UniversityDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai UniversityResearch Center for Drug and Vaccine Development, National Institute of Infectious DiseasesAbstract Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated the neutralizing activity of recalled antibodies, primarily targeting an immunodominant site III epitope with hydrophilic and rugged structures. Strikingly, the majority of site III-directed antibodies in the recall response used a convergent VH gene (IGHV3-30), and they exhibited more hydrophilic and shorter paratopes than non-site III antibodies, providing physicochemical advantages for binding to site III. Additionally, several amino acids on heavy chain CDR3 were identified as key sites for acquiring an ultrapotent neutralizing activity through site III binding. Our in-depth analysis of antibody repertoires revealed the molecular signatures of neutralizing antibodies generated by repeated rabies vaccination, possibly as a result of adaptive convergence.https://doi.org/10.1038/s41541-025-01073-5 |
| spellingShingle | Mizuki Fujisawa Taishi Onodera Daisuke Kuroda Chidchamai Kewcharoenwong Michihito Sasaki Yukari Itakura Kohei Yumoto Arnone Nithichanon Naoto Ito Shinji Takeoka Tadaki Suzuki Hirofumi Sawa Ganjana Lertmemongkolchai Yoshimasa Takahashi Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination npj Vaccines |
| title | Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| title_full | Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| title_fullStr | Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| title_full_unstemmed | Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| title_short | Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| title_sort | molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination |
| url | https://doi.org/10.1038/s41541-025-01073-5 |
| work_keys_str_mv | AT mizukifujisawa molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT taishionodera molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT daisukekuroda molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT chidchamaikewcharoenwong molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT michihitosasaki molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT yukariitakura molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT koheiyumoto molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT arnonenithichanon molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT naotoito molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT shinjitakeoka molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT tadakisuzuki molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT hirofumisawa molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT ganjanalertmemongkolchai molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination AT yoshimasatakahashi molecularconvergenceofneutralizingantibodiesinhumanrevealedbyrepeatedrabiesvaccination |