Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model
Pertussis has been resurgent in many countries worldwide despite good vaccine coverage. One hypothesis for this resurgence is that the current acellular pertussis (aP) vaccines, used in most developed countries, induce short-term protection, and do not prevent asymptomatic infection and transmission...
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Elsevier
2025-06-01
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| Series: | Vaccine: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590136225000531 |
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| author | Alexa Dierig Martina Kristof Christina Dold Elodie Lesne Catpagavalli Asokanathan Luke Blackwell Barbara Bolgiano Andrew R. Gorringe Andrew J. Pollard Kevin Markey Christine S. Rollier |
| author_facet | Alexa Dierig Martina Kristof Christina Dold Elodie Lesne Catpagavalli Asokanathan Luke Blackwell Barbara Bolgiano Andrew R. Gorringe Andrew J. Pollard Kevin Markey Christine S. Rollier |
| author_sort | Alexa Dierig |
| collection | DOAJ |
| description | Pertussis has been resurgent in many countries worldwide despite good vaccine coverage. One hypothesis for this resurgence is that the current acellular pertussis (aP) vaccines, used in most developed countries, induce short-term protection, and do not prevent asymptomatic infection and transmission of pertussis infection. As a first step to address these issues we developed novel Bordetella pertussis vaccine candidates using viral-vectored vaccine technology with the aim of producing durable functional antibodies that prevent nasal colonization. Fimbrial antigens Fim2 and Fim3 are protective in mouse models of B. pertussis disease and are included in some aP vaccines. Fim2, Fim3 and FimD were selected, and their genes cloned into entry plasmids for the creation of the corresponding human adenovirus serotype 5 (AdHu5) vectors. Groups of mice were vaccinated with a single dose of either of the three AdHu5 vaccines, or a mixture of them, or control vaccines, which consisted of one or two reduced doses of a whole-cell pertussis vaccine or 5-component aP vaccine. The Fim2 and Fim3 adenovirus-based vaccines and their combinations alone or with FimD induced antigen-specific antibodies, as assessed by whole cell ELISA assay. Strong IgG binding to a Fim3-expressing strain was observed using flow cytometry and these antibodies also mediated complement deposition onto this strain. The AdHu5 Fim3 vaccine induced partial protection against lung infection following aerosol exposure of mice to B. pertussis expressing Fim3. These results indicate that adenovirus vectors have the potential to be effective vaccine platforms for bacterial disease. |
| format | Article |
| id | doaj-art-ed30ee40e9d34137b99789dd6b29b19e |
| institution | OA Journals |
| issn | 2590-1362 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Vaccine: X |
| spelling | doaj-art-ed30ee40e9d34137b99789dd6b29b19e2025-08-20T02:05:12ZengElsevierVaccine: X2590-13622025-06-012410065910.1016/j.jvacx.2025.100659Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse modelAlexa Dierig0Martina Kristof1Christina Dold2Elodie Lesne3Catpagavalli Asokanathan4Luke Blackwell5Barbara Bolgiano6Andrew R. Gorringe7Andrew J. Pollard8Kevin Markey9Christine S. Rollier10Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UKOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UK; Science and Research, Medicines and Healthcare products Regulatory Agency, South Mimms, UKOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UKUK Health Security Agency, Porton Down, Salisbury, UKScience and Research, Medicines and Healthcare products Regulatory Agency, South Mimms, UKOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UKScience and Research, Medicines and Healthcare products Regulatory Agency, South Mimms, UKUK Health Security Agency, Porton Down, Salisbury, UKOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UKScience and Research, Medicines and Healthcare products Regulatory Agency, South Mimms, UK; Corresponding author.Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, CCVTM, Oxford, UK; School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UKPertussis has been resurgent in many countries worldwide despite good vaccine coverage. One hypothesis for this resurgence is that the current acellular pertussis (aP) vaccines, used in most developed countries, induce short-term protection, and do not prevent asymptomatic infection and transmission of pertussis infection. As a first step to address these issues we developed novel Bordetella pertussis vaccine candidates using viral-vectored vaccine technology with the aim of producing durable functional antibodies that prevent nasal colonization. Fimbrial antigens Fim2 and Fim3 are protective in mouse models of B. pertussis disease and are included in some aP vaccines. Fim2, Fim3 and FimD were selected, and their genes cloned into entry plasmids for the creation of the corresponding human adenovirus serotype 5 (AdHu5) vectors. Groups of mice were vaccinated with a single dose of either of the three AdHu5 vaccines, or a mixture of them, or control vaccines, which consisted of one or two reduced doses of a whole-cell pertussis vaccine or 5-component aP vaccine. The Fim2 and Fim3 adenovirus-based vaccines and their combinations alone or with FimD induced antigen-specific antibodies, as assessed by whole cell ELISA assay. Strong IgG binding to a Fim3-expressing strain was observed using flow cytometry and these antibodies also mediated complement deposition onto this strain. The AdHu5 Fim3 vaccine induced partial protection against lung infection following aerosol exposure of mice to B. pertussis expressing Fim3. These results indicate that adenovirus vectors have the potential to be effective vaccine platforms for bacterial disease.http://www.sciencedirect.com/science/article/pii/S2590136225000531Bordetella pertussisVaccineFimbriaeAdenovirusViral-vectored vaccineGene-based vaccine |
| spellingShingle | Alexa Dierig Martina Kristof Christina Dold Elodie Lesne Catpagavalli Asokanathan Luke Blackwell Barbara Bolgiano Andrew R. Gorringe Andrew J. Pollard Kevin Markey Christine S. Rollier Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model Vaccine: X Bordetella pertussis Vaccine Fimbriae Adenovirus Viral-vectored vaccine Gene-based vaccine |
| title | Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| title_full | Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| title_fullStr | Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| title_full_unstemmed | Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| title_short | Adenoviral-vectored vaccine against Bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| title_sort | adenoviral vectored vaccine against bordetella pertussis fimbrial antigen induces partial protection in a mouse model |
| topic | Bordetella pertussis Vaccine Fimbriae Adenovirus Viral-vectored vaccine Gene-based vaccine |
| url | http://www.sciencedirect.com/science/article/pii/S2590136225000531 |
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