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Full Brain and Lung Prophylaxis against SARS-CoV-2 by Intranasal Lentiviral Vaccination in a New hACE2 Transgenic Mouse Model or Golden Hamsters
Min-Wen Ku; Pierre Authie; Maryline Bourgine; Francois Anna; Amandine Noirat; Fanny Moncoq; Benjamin Vesin; Fabien Nevo; Jodie Lopez; Philippe Souque; Catherine Blanc; Sebastien Chardenoux; Ilta Lafosse; David Hardy; Kirill Nemirov; Francoise Guinet; Francina Langa Vives; Laleh Majlessi; Pierre Charneau.
  • Min-Wen Ku; Institut Pasteur-TheraVectys Joint Lab
  • Pierre Authie; Institut Pasteur-TheraVectys Joint Lab
  • Maryline Bourgine; Institut Pasteur
  • Francois Anna; Institut Pasteur-TheraVectys Joint Lab
  • Amandine Noirat; Institut Pasteur-TheraVectys Joint Lab
  • Fanny Moncoq; Institut Pasteur-TheraVectys Joint Lab
  • Benjamin Vesin; Institut Pasteur-TheraVectys Joint Lab
  • Fabien Nevo; Institut Pasteur-TheraVectys Joint Lab
  • Jodie Lopez; Institut Pasteur-TheraVectys Joint Lab
  • Philippe Souque; Institut Pasteur
  • Catherine Blanc; Institut Pasteur
  • Sebastien Chardenoux; Institut Pasteur
  • Ilta Lafosse; Institut Pasteur
  • David Hardy; Institut Pasteur
  • Kirill Nemirov; Institut Pasteur-TheraVectys Joint Lab
  • Francoise Guinet; Institut Pasteur
  • Francina Langa Vives; Institut Pasteur
  • Laleh Majlessi; Institut Pasteur
  • Pierre Charneau; Institut Pasteur
Preprint in English | bioRxiv | ID: ppbiorxiv-429211
ABSTRACT
Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors are particularly suitable for mucosal vaccination and recently emerge as a promising strategy to elicit sterilizing prophylaxis against SARS-CoV-2 in preclinical animal models. Here, we demonstrate that a single intranasal administration of a lentiviral vector encoding a prefusion form of SARS-CoV-2 spike glycoprotein induces full protection of respiratory tracts and totally avoids pulmonary inflammation in the susceptible hamster model. More importantly, we generated a new transgenic mouse strain, expressing the human Angiotensin Converting Enzyme 2, with unprecedent brain permissibility to SARS-CoV-2 replication and developing a lethal disease in <4 days post infection. Even though the neurotropism of SARS-CoV-2 is now well established, so far other vaccine strategies under development have not taken into the account the protection of central nervous system. Using our highly stringent transgenic model, we demonstrated that an intranasal booster immunization with the developed lentiviral vaccine candidate achieves full protection of both respiratory tracts and brain against SARS-CoV-2.
Full text: Available Collection: Preprints Database: bioRxiv Topics: Vaccines Language: English Year: 2021 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Topics: Vaccines Language: English Year: 2021 Document Type: Preprint