Brain cross-protection against SARS-CoV-2 variants by a lentiviral vaccine in new transgenic mice.
EMBO Mol Med
; 13(12): e14459, 2021 12 07.
Article
in English
| MEDLINE | ID: covidwho-1468845
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
EMBO Mol Med
Journal subject:
Molecular Biology
Year:
2021
Document Type:
Article
Affiliation country:
Emmm.202114459
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