publication . Article . 2021

Brain Cross‐Protection against SARS‐CoV‐2 Variants by a Lentiviral Vaccine in New Transgenic Mice

Min-Wen Ku; Pierre Authié; Maryline Bourgine; François Anna; Amandine Noirat; Fanny Moncoq; Benjamin Vesin; Fabien Nevo; Jodie Lopez; Philippe Souque; ...
Open Access English
  • Published: 14 Oct 2021
  • Publisher: HAL CCSD
  • Country: France
Abstract
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.
A lentiviral vector‐based vaccine, used in prime and intranasal boost, induces strong B‐ and T‐cell immunity. This vaccine candidate protects against both pulmonary and neurological COVID‐19 caused by either ancestral or emerging SARS‐CoV‐2.
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free text keywords: Central Nervous System, Intranasal Vaccination, Olfactory Bulb, SARS-CoV-2 Emerging Variants of Concern, hACE2 Transgenic Mice, [SDV]Life Sciences [q-bio], Molecular Medicine, Article, Articles, SARS‐CoV‐2 emerging variants of concern, Immunology, Microbiology, Virology & Host Pathogen Interaction, Medicine (General), R5-920, Genetics, QH426-470, Transgenic Model, Antibody, biology.protein, biology, Virology, Neurotropism, Permissiveness, Virus, Genetically modified mouse, Immunity, Viral vector
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