YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge
Abstract Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vect...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00699-7 |
| _version_ | 1797415910249594880 |
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| author | Viktor Lemmens Lara Kelchtermans Sarah Debaveye Winston Chiu Thomas Vercruysse Ji Ma Hendrik Jan Thibaut Johan Neyts Lorena Sanchez-Felipe Kai Dallmeier |
| author_facet | Viktor Lemmens Lara Kelchtermans Sarah Debaveye Winston Chiu Thomas Vercruysse Ji Ma Hendrik Jan Thibaut Johan Neyts Lorena Sanchez-Felipe Kai Dallmeier |
| author_sort | Viktor Lemmens |
| collection | DOAJ |
| description | Abstract Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV GP-specific antibodies and cellular immune responses, that protected against lethal infection using EBOV GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar -/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar -/- mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of the 2022 outbreak in Uganda. |
| first_indexed | 2024-03-09T05:56:16Z |
| format | Article |
| id | doaj.art-6df8991fb9124a22ae07f96ee394ac98 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T05:56:16Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-6df8991fb9124a22ae07f96ee394ac982023-12-03T12:13:16ZengNature Portfolionpj Vaccines2059-01052023-07-018111210.1038/s41541-023-00699-7YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challengeViktor Lemmens0Lara Kelchtermans1Sarah Debaveye2Winston Chiu3Thomas Vercruysse4Ji Ma5Hendrik Jan Thibaut6Johan Neyts7Lorena Sanchez-Felipe8Kai Dallmeier9KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC)KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC)KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine DiscoveryAbstract Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV GP-specific antibodies and cellular immune responses, that protected against lethal infection using EBOV GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar -/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar -/- mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of the 2022 outbreak in Uganda.https://doi.org/10.1038/s41541-023-00699-7 |
| spellingShingle | Viktor Lemmens Lara Kelchtermans Sarah Debaveye Winston Chiu Thomas Vercruysse Ji Ma Hendrik Jan Thibaut Johan Neyts Lorena Sanchez-Felipe Kai Dallmeier YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge npj Vaccines |
| title | YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge |
| title_full | YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge |
| title_fullStr | YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge |
| title_full_unstemmed | YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge |
| title_short | YF17D-vectored Ebola vaccine candidate protects mice against lethal surrogate Ebola and yellow fever virus challenge |
| title_sort | yf17d vectored ebola vaccine candidate protects mice against lethal surrogate ebola and yellow fever virus challenge |
| url | https://doi.org/10.1038/s41541-023-00699-7 |
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