A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector
In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field o...
| Published in: | Vaccines |
|---|---|
| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/2/241 |
| _version_ | 1850410732142723072 |
|---|---|
| author | Sarah Sebastian Amy Flaxman Kuan M. Cha Marta Ulaszewska Ciaran Gilbride Hannah Sharpe Edward Wright Alexandra J. Spencer Stuart Dowall Roger Hewson Sarah Gilbert Teresa Lambe |
| author_facet | Sarah Sebastian Amy Flaxman Kuan M. Cha Marta Ulaszewska Ciaran Gilbride Hannah Sharpe Edward Wright Alexandra J. Spencer Stuart Dowall Roger Hewson Sarah Gilbert Teresa Lambe |
| author_sort | Sarah Sebastian |
| collection | DOAJ |
| container_title | Vaccines |
| description | In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate based on a replication-deficient simian adenoviral vector. Our vaccine candidate encodes three different filovirus glycoproteins in one vector and induces strong cellular and humoral immunity to all three viral glycoproteins after a single vaccination. Crucially, it was found to be protective in a stringent Zaire ebolavirus challenge in guinea pigs in a one-shot vaccination regimen. This trivalent filovirus vaccine offers a tenable vaccine product that could be rapidly translated to the clinic to prevent filovirus-mediated viral haemorrhagic fever. |
| format | Article |
| id | doaj-art-cebb7ed441bf4e5398205c31e2c1da44 |
| institution | Directory of Open Access Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-cebb7ed441bf4e5398205c31e2c1da442025-08-19T22:46:50ZengMDPI AGVaccines2076-393X2020-05-018224110.3390/vaccines8020241A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single VectorSarah Sebastian0Amy Flaxman1Kuan M. Cha2Marta Ulaszewska3Ciaran Gilbride4Hannah Sharpe5Edward Wright6Alexandra J. Spencer7Stuart Dowall8Roger Hewson9Sarah Gilbert10Teresa Lambe11Nuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKSchool of Life Sciences, University of Sussex, Falmer BN1 9QG, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKPublic Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UKPublic Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKNuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKIn the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate based on a replication-deficient simian adenoviral vector. Our vaccine candidate encodes three different filovirus glycoproteins in one vector and induces strong cellular and humoral immunity to all three viral glycoproteins after a single vaccination. Crucially, it was found to be protective in a stringent Zaire ebolavirus challenge in guinea pigs in a one-shot vaccination regimen. This trivalent filovirus vaccine offers a tenable vaccine product that could be rapidly translated to the clinic to prevent filovirus-mediated viral haemorrhagic fever.https://www.mdpi.com/2076-393X/8/2/241EbolaMarburgfilovirusvaccineviral vector |
| spellingShingle | Sarah Sebastian Amy Flaxman Kuan M. Cha Marta Ulaszewska Ciaran Gilbride Hannah Sharpe Edward Wright Alexandra J. Spencer Stuart Dowall Roger Hewson Sarah Gilbert Teresa Lambe A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector Ebola Marburg filovirus vaccine viral vector |
| title | A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector |
| title_full | A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector |
| title_fullStr | A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector |
| title_full_unstemmed | A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector |
| title_short | A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector |
| title_sort | multi filovirus vaccine candidate co expression of ebola sudan and marburg antigens in a single vector |
| topic | Ebola Marburg filovirus vaccine viral vector |
| url | https://www.mdpi.com/2076-393X/8/2/241 |
| work_keys_str_mv | AT sarahsebastian amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT amyflaxman amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT kuanmcha amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT martaulaszewska amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT ciarangilbride amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT hannahsharpe amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT edwardwright amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT alexandrajspencer amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT stuartdowall amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT rogerhewson amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT sarahgilbert amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT teresalambe amultifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT sarahsebastian multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT amyflaxman multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT kuanmcha multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT martaulaszewska multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT ciarangilbride multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT hannahsharpe multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT edwardwright multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT alexandrajspencer multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT stuartdowall multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT rogerhewson multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT sarahgilbert multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector AT teresalambe multifilovirusvaccinecandidatecoexpressionofebolasudanandmarburgantigensinasinglevector |