Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus
Abstract Background Disease caused by the capsular group B meningococcus (MenB) is the leading cause of infectious death in UK infants. A novel adenovirus-based vaccine encoding the MenB factor H binding protein (fHbp) with an N-terminal dual signal sequence induces high titres of protective antibod...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-022-00809-3 |
| _version_ | 1811247878906052608 |
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| author | Dylan Sheerin Christina Dold Laura Silva-Reyes Aline Linder Andrew J. Pollard Christine S. Rollier |
| author_facet | Dylan Sheerin Christina Dold Laura Silva-Reyes Aline Linder Andrew J. Pollard Christine S. Rollier |
| author_sort | Dylan Sheerin |
| collection | DOAJ |
| description | Abstract Background Disease caused by the capsular group B meningococcus (MenB) is the leading cause of infectious death in UK infants. A novel adenovirus-based vaccine encoding the MenB factor H binding protein (fHbp) with an N-terminal dual signal sequence induces high titres of protective antibody after a single dose in mice. A panel of N-terminal signal sequence variants were created to assess the contribution of components of this sequence to transgene expression kinetics of the encoded antigen from mammalian cells and the resultant effect on immunogenicity of fHbp. Results The full-length signal sequence (FL SS) resulted in superior early antigen expression compared with the panel of variants, as measured by flow cytometry and confocal imaging, and supported higher bactericidal antibody levels against the expressed antigen in mouse sera < 6 weeks post-immunisation than the licensed four component MenB vaccine. The FL SS also significantly increased antigen-specific T cell responses against other adenovirus-encoded bacterial antigens in mice. Conclusions These findings demonstrate that the FL SS enhances immunogenicity of the encoded antigen, supporting its inclusion in other viral vectored bacterial antigen transgenes. |
| first_indexed | 2024-04-12T15:17:14Z |
| format | Article |
| id | doaj.art-2a8c2c533c3841199f718f77b56644e4 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-12T15:17:14Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-2a8c2c533c3841199f718f77b56644e42022-12-22T03:27:35ZengBMCCell & Bioscience2045-37012022-06-0112111510.1186/s13578-022-00809-3Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcusDylan Sheerin0Christina Dold1Laura Silva-Reyes2Aline Linder3Andrew J. Pollard4Christine S. Rollier5Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalAbstract Background Disease caused by the capsular group B meningococcus (MenB) is the leading cause of infectious death in UK infants. A novel adenovirus-based vaccine encoding the MenB factor H binding protein (fHbp) with an N-terminal dual signal sequence induces high titres of protective antibody after a single dose in mice. A panel of N-terminal signal sequence variants were created to assess the contribution of components of this sequence to transgene expression kinetics of the encoded antigen from mammalian cells and the resultant effect on immunogenicity of fHbp. Results The full-length signal sequence (FL SS) resulted in superior early antigen expression compared with the panel of variants, as measured by flow cytometry and confocal imaging, and supported higher bactericidal antibody levels against the expressed antigen in mouse sera < 6 weeks post-immunisation than the licensed four component MenB vaccine. The FL SS also significantly increased antigen-specific T cell responses against other adenovirus-encoded bacterial antigens in mice. Conclusions These findings demonstrate that the FL SS enhances immunogenicity of the encoded antigen, supporting its inclusion in other viral vectored bacterial antigen transgenes.https://doi.org/10.1186/s13578-022-00809-3Meningococcal diseaseViral vector vaccinesSignal sequenceTransgeneExpression kinetics |
| spellingShingle | Dylan Sheerin Christina Dold Laura Silva-Reyes Aline Linder Andrew J. Pollard Christine S. Rollier Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus Cell & Bioscience Meningococcal disease Viral vector vaccines Signal sequence Transgene Expression kinetics |
| title | Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus |
| title_full | Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus |
| title_fullStr | Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus |
| title_full_unstemmed | Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus |
| title_short | Inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group B meningococcus |
| title_sort | inclusion of a dual signal sequence enhances the immunogenicity of a novel viral vectored vaccine against the capsular group b meningococcus |
| topic | Meningococcal disease Viral vector vaccines Signal sequence Transgene Expression kinetics |
| url | https://doi.org/10.1186/s13578-022-00809-3 |
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