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Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models.
Ku, Min-Wen; Bourgine, Maryline; Authié, Pierre; Lopez, Jodie; Nemirov, Kirill; Moncoq, Fanny; Noirat, Amandine; Vesin, Benjamin; Nevo, Fabien; Blanc, Catherine; Souque, Philippe; Tabbal, Houda; Simon, Emeline; Hardy, David; Le Dudal, Marine; Guinet, Françoise; Fiette, Laurence; Mouquet, Hugo; Anna, François; Martin, Annette; Escriou, Nicolas; Majlessi, Laleh; Charneau, Pierre.
Affiliation
  • Ku MW; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Bourgine M; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France; Molecular Virology and Vaccinology Unit, Virology Department, Institut Pasteur, Paris 75015, France.
  • Authié P; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Lopez J; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Nemirov K; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Moncoq F; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Noirat A; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Vesin B; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Nevo F; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Blanc C; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Souque P; Molecular Virology and Vaccinology Unit, Virology Department, Institut Pasteur, Paris 75015, France.
  • Tabbal H; Molecular Genetics of RNA Viruses Unit, Virology Department, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris 75015, France.
  • Simon E; Molecular Genetics of RNA Viruses Unit, Virology Department, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris 75015, France; Université de Paris, Paris 75006, France.
  • Hardy D; Experimental Neuropathology Unit, Global Health Department, Institut Pasteur, Paris 75015, France.
  • Le Dudal M; IMMR, 42 boulevard Jourdan, Paris 75014, France.
  • Guinet F; Lymphocytes and Immunity Unit, Immunology Department, Institut Pasteur, Paris 75015, France.
  • Fiette L; IMMR, 42 boulevard Jourdan, Paris 75014, France.
  • Mouquet H; Laboratory of Humoral Immunology, Immunology Department, Institut Pasteur, INSERM U1222, Paris, France.
  • Anna F; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
  • Martin A; Molecular Genetics of RNA Viruses Unit, Virology Department, Institut Pasteur, CNRS UMR3569, Université de Paris, Paris 75015, France.
  • Escriou N; Innovation Lab, Vaccines, Virology Department, Institut Pasteur, Paris 75015, France.
  • Majlessi L; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France. Electronic address: laleh.majlessi@pasteur.fr.
  • Charneau P; Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France; Molecular Virology and Vaccinology Unit, Virology Department, Institut Pasteur, Paris 75015, France. Electronic address: pierre.charneau@pasteur.fr.
Cell Host Microbe ; 29(2): 236-249.e6, 2021 02 10.
Article in En | MEDLINE | ID: mdl-33357418
ABSTRACT
To develop a vaccine candidate against coronavirus disease 2019 (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, confers only partial protection despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in a >3 log10 decrease in the lung viral loads and reduces local inflammation. Moreover, both integrative and non-integrative LV platforms display strong vaccine efficacy and inhibit lung deleterious injury in golden hamsters, which are naturally permissive to SARS-CoV-2 replication and closely mirror human COVID-19 physiopathology. Our results provide evidence of marked prophylactic effects of LV-based vaccination against SARS-CoV-2 and designate intranasal immunization as a powerful approach against COVID-19.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Administration, Intranasal / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Limits: Animals Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2021 Document type: Article Affiliation country: France
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Administration, Intranasal / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Limits: Animals Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2021 Document type: Article Affiliation country: France