Intranasal Vaccination with a Lentiviral Vector Strongly Protects against SARS-CoV-2 in Mouse and Golden Hamster Preclinical 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; Le Dudal, Marine; Guinet, Françoise; Fiette, Laurence; Mouquet, Hugo; Anna, François; Martin, Annette; Escriou, Nicolas; Majlessi, Laleh; Charneau, Pierre

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. Highlights A 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