Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice
Abstract COVID‐19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS‐CoV‐2 variants. In addition, although the neurotropism of SARS‐CoV‐2 is well established, the vaccine strategies currently developed have not taken into account protection of the cent...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114459 |
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| author | Min‐Wen Ku Pierre Authié Maryline Bourgine François Anna Amandine Noirat Fanny Moncoq Benjamin Vesin Fabien Nevo Jodie Lopez Philippe Souque Catherine Blanc Ingrid Fert Sébastien Chardenoux llta Lafosse Delphine Cussigh David Hardy Kirill Nemirov Françoise Guinet Francina Langa Vives Laleh Majlessi Pierre Charneau |
| author_facet | Min‐Wen Ku Pierre Authié Maryline Bourgine François Anna Amandine Noirat Fanny Moncoq Benjamin Vesin Fabien Nevo Jodie Lopez Philippe Souque Catherine Blanc Ingrid Fert Sébastien Chardenoux llta Lafosse Delphine Cussigh David Hardy Kirill Nemirov Françoise Guinet Francina Langa Vives Laleh Majlessi Pierre Charneau |
| author_sort | Min‐Wen Ku |
| collection | DOAJ |
| description | Abstract COVID‐19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS‐CoV‐2 variants. In addition, although the neurotropism of SARS‐CoV‐2 is well established, the vaccine strategies currently developed have not taken into account protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human angiotensin‐converting enzyme 2, and displaying unprecedented brain permissiveness to SARS‐CoV‐2 replication, in addition to high permissiveness levels in the lung. Using this stringent transgenic model, we demonstrated that a non‐integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral SARS‐CoV‐2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the ancestral virus, and the Gamma (P.1) variant of concern, which carries multiple vaccine escape mutations. Beyond induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective T‐cell immunity, unaffected by the recent mutations accumulated in the emerging SARS‐CoV‐2 variants. |
| format | Article |
| id | doaj-art-e281ac5ccf5c4d798e95aba80cc3ff64 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e281ac5ccf5c4d798e95aba80cc3ff642025-08-20T04:03:06ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-10-01131212110.15252/emmm.202114459Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic miceMin‐Wen Ku0Pierre Authié1Maryline Bourgine2François Anna3Amandine Noirat4Fanny Moncoq5Benjamin Vesin6Fabien Nevo7Jodie Lopez8Philippe Souque9Catherine Blanc10Ingrid Fert11Sébastien Chardenoux12llta Lafosse13Delphine Cussigh14David Hardy15Kirill Nemirov16Françoise Guinet17Francina Langa Vives18Laleh Majlessi19Pierre Charneau20Virology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabPlate‐Forme Centre d'Ingénierie Génétique Murine CIGM, Institut PasteurPlate‐Forme Centre d'Ingénierie Génétique Murine CIGM, Institut PasteurPlate‐Forme Centre d'Ingénierie Génétique Murine CIGM, Institut PasteurExperimental Neuropatholgy Unit, Institut PasteurVirology Department, Institut Pasteur‐TheraVectys Joint LabLymphocytes and Immunity Unit, Immunology Department, Institut PasteurPlate‐Forme Centre d'Ingénierie Génétique Murine CIGM, Institut PasteurVirology Department, Institut Pasteur‐TheraVectys Joint LabVirology Department, Institut Pasteur‐TheraVectys Joint LabAbstract COVID‐19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS‐CoV‐2 variants. In addition, although the neurotropism of SARS‐CoV‐2 is well established, the vaccine strategies currently developed have not taken into account protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human angiotensin‐converting enzyme 2, and displaying unprecedented brain permissiveness to SARS‐CoV‐2 replication, in addition to high permissiveness levels in the lung. Using this stringent transgenic model, we demonstrated that a non‐integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral SARS‐CoV‐2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the ancestral virus, and the Gamma (P.1) variant of concern, which carries multiple vaccine escape mutations. Beyond induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective T‐cell immunity, unaffected by the recent mutations accumulated in the emerging SARS‐CoV‐2 variants.https://doi.org/10.15252/emmm.202114459central nervous systemhACE2 transgenic miceintranasal vaccinationolfactory bulbSARS‐CoV‐2 emerging variants of concern |
| spellingShingle | Min‐Wen Ku Pierre Authié Maryline Bourgine François Anna Amandine Noirat Fanny Moncoq Benjamin Vesin Fabien Nevo Jodie Lopez Philippe Souque Catherine Blanc Ingrid Fert Sébastien Chardenoux llta Lafosse Delphine Cussigh David Hardy Kirill Nemirov Françoise Guinet Francina Langa Vives Laleh Majlessi Pierre Charneau Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice EMBO Molecular Medicine central nervous system hACE2 transgenic mice intranasal vaccination olfactory bulb SARS‐CoV‐2 emerging variants of concern |
| title | Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice |
| title_full | Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice |
| title_fullStr | Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice |
| title_full_unstemmed | Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice |
| title_short | Brain cross‐protection against SARS‐CoV‐2 variants by a lentiviral vaccine in new transgenic mice |
| title_sort | brain cross protection against sars cov 2 variants by a lentiviral vaccine in new transgenic mice |
| topic | central nervous system hACE2 transgenic mice intranasal vaccination olfactory bulb SARS‐CoV‐2 emerging variants of concern |
| url | https://doi.org/10.15252/emmm.202114459 |
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