Journal
EMBO MOLECULAR MEDICINE
Volume 13, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202114459
Keywords
central nervous system; hACE2 transgenic mice; intranasal vaccination; olfactory bulb; SARS-CoV-2 emerging variants of concern
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Funding
- European Union [653316]
- URGENCE COVID-19 fundraising campaign of Institut Pasteur
- TheraVectys
- Agence Nationale de la Recherche (ANR) HuMoCID
- Institut Carnot Pasteur Microbes Sante
- European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant [665807]
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Research has shown that using a non-integrative lentiviral vector to inject the spike glycoprotein of the ancestral SARS-CoV-2 can provide sterilizing protection of the lung and brain against both the ancestral virus and the Gamma variant carrying multiple vaccine escape mutations.
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.
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