• Min-Wen Ku, Maryline Bourgine, Pierre Authié, Jodie Lopez, Kirill Nemirov, Fanny Moncoq, Amandine Noirat, Benjamin Vesin, Fabien Nevo, Catherine Blanc, Philippe Souque, Houda Tabbal, Emeline Simon, David Hardy, Marine Le Dudal, Françoise Guinet, Laurence Fiette, Hugo Mouquet, François Anna, Annette Martin, Nicolas Escriou, Laleh Majlessi, and Pierre Charneau.
• Institut Pasteur-TheraVectys Joint Lab, Virology Department, Institut Pasteur, Paris 75015, France.
• Cell Host Microbe. 2021 Feb 10; 29 (2): 236-249.e6.

AbstractTo 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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