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Intranasal Immunization with a Lentiviral Vector Coding for SARS-CoV-2 Spike Protein Confers Vigorous Protection in Pre-Clinical Animal Models
Min-Wen Ku; Maryline Bourgine; Pierre Authie; Jodie Lopez; Kirill Nemirov; Fanny Moncoq; Amandine Noirat; Benjamin Vesin; Fabien Nevo; Catherine Blanc; Philippe Souque; Houda Tabbal; Emeline Simon; Marine Le Dudal; Francoise Guinet; Laurence Fiette; Hugo Mouquet; Francois Anna; Annette Martin; Nicolas Escriou; Laleh Majlessi; Pierre Charneau.
  • Min-Wen Ku; Institut Pasteur
  • Maryline Bourgine; Institut Pasteur
  • Pierre Authie; Institut Pasteur - TheraVectys
  • Jodie Lopez; Institut Pasteur - TheraVectys
  • Kirill Nemirov; Institut Pasteur - TheraVectys
  • Fanny Moncoq; Institut Pasteur - TheraVectys
  • Amandine Noirat; Institut Pasteur - Theravectys
  • Benjamin Vesin; Institut Pasteur - TheraVectys
  • Fabien Nevo; Institut Pasteur - TheraVectys
  • Catherine Blanc; Institut Pasteur
  • Philippe Souque; Institut Pasteur
  • Houda Tabbal; Institut Pasteur
  • Emeline Simon; Institut Pasteur
  • Marine Le Dudal; IMMR
  • Francoise Guinet; Institut Pasteur
  • Laurence Fiette; IMMR
  • Hugo Mouquet; Institut Pasteur
  • Francois Anna; Institut Pasteur - TheraVectys
  • Annette Martin; Institut Pasteur
  • Nicolas Escriou; Institut Pasteur
  • Laleh Majlessi; Institut Pasteur
  • Pierre Charneau; Institut Pasteur - TheraVectys
Preprint in English | bioRxiv | ID: ppbiorxiv-214049
ABSTRACT
To develop a vaccine candidate against COVID-19, we generated a Lentiviral Vector (LV), eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, conferred only partial protection, despite an intense serum neutralizing activity. However, targeting the immune response to the respiratory tract through an intranasal boost with this LV resulted in > 3 log10 decrease in the lung viral loads and avoided local inflammation. Moreover, both integrative and non-integrative LV platforms displayed a strong vaccine efficacy and inhibited lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and restitute the human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of the LV-based vaccination against SARS-CoV-2 and designate the intranasal immunization as a powerful approach against COVID-19. HighlightsA lentiviral vector encoding for Spike predicts a promising COVID-19 vaccine Targeting the immune response to the upper respiratory tract is key to protection Intranasal vaccination induces protective mucosal immunity against SARS-CoV-2 Lung anti-Spike IgA responses correlate with protection and reduced inflammation
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Topics: Vaccines Language: English Year: 2020 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Topics: Vaccines Language: English Year: 2020 Document Type: Preprint