Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae
Abstract Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. Howeve...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-01054-0 |
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| author | Jamie E. Fegan Epshita A. Islam David M. Curran Dixon Ng Natalie Y. T. Au Elissa G. Currie Joseph J. Zeppa Jessica Lam Anthony B. Schryvers Trevor F. Moraes Scott D. Gray-Owen |
| author_facet | Jamie E. Fegan Epshita A. Islam David M. Curran Dixon Ng Natalie Y. T. Au Elissa G. Currie Joseph J. Zeppa Jessica Lam Anthony B. Schryvers Trevor F. Moraes Scott D. Gray-Owen |
| author_sort | Jamie E. Fegan |
| collection | DOAJ |
| description | Abstract Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a gonococcal vaccine and identify two TbpB variants that together elicit a highly cross-reactive antibody response against a diverse panel of TbpB variants and clinically relevant gonococcal strains. This formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice. These data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine. |
| format | Article |
| id | doaj-art-fb09957133994336817e9a26b644f9e9 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-fb09957133994336817e9a26b644f9e92025-01-19T12:09:19ZengNature Portfolionpj Vaccines2059-01052025-01-0110111410.1038/s41541-024-01054-0Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeaeJamie E. Fegan0Epshita A. Islam1David M. Curran2Dixon Ng3Natalie Y. T. Au4Elissa G. Currie5Joseph J. Zeppa6Jessica Lam7Anthony B. Schryvers8Trevor F. Moraes9Scott D. Gray-Owen10Department of Molecular Genetics, Temerty Faculty of Medicine, University of TorontoDepartment of Biochemistry, Temerty Faculty of Medicine, University of TorontoDepartment of Biochemistry, Temerty Faculty of Medicine, University of TorontoDepartment of Biochemistry, Temerty Faculty of Medicine, University of TorontoDepartment of Biochemistry, Temerty Faculty of Medicine, University of TorontoDepartment of Molecular Genetics, Temerty Faculty of Medicine, University of TorontoDepartment of Molecular Genetics, Temerty Faculty of Medicine, University of TorontoDepartment of Molecular Genetics, Temerty Faculty of Medicine, University of TorontoDepartment of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of CalgaryDepartment of Biochemistry, Temerty Faculty of Medicine, University of TorontoDepartment of Molecular Genetics, Temerty Faculty of Medicine, University of TorontoAbstract Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a gonococcal vaccine and identify two TbpB variants that together elicit a highly cross-reactive antibody response against a diverse panel of TbpB variants and clinically relevant gonococcal strains. This formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice. These data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine.https://doi.org/10.1038/s41541-024-01054-0 |
| spellingShingle | Jamie E. Fegan Epshita A. Islam David M. Curran Dixon Ng Natalie Y. T. Au Elissa G. Currie Joseph J. Zeppa Jessica Lam Anthony B. Schryvers Trevor F. Moraes Scott D. Gray-Owen Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae npj Vaccines |
| title | Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae |
| title_full | Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae |
| title_fullStr | Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae |
| title_full_unstemmed | Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae |
| title_short | Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae |
| title_sort | rational selection of tbpb variants yields a bivalent vaccine with broad coverage against neisseria gonorrhoeae |
| url | https://doi.org/10.1038/s41541-024-01054-0 |
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