Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models.

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 log 10 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. • A lentiviral vector encoding Spike shows preclinical efficacy as a COVID-19 vaccine • Targeting the immune response to the upper respiratory tract provides critical protection • Intranasal vaccination induces protective mucosal immunity against SARS-CoV-2 in rodents • Lung anti-Spike IgA responses correlate with protection and reduced inflammation Ku et al. present a lentiviral vaccination vector that encodes a full-length, membrane-anchored form of SARS-CoV-2 Spike glycoprotein and induces neutralizing antibodies and T cell responses. An intranasal boost strategy triggers a localized immune response in the upper respiratory tract that provides disease protection in mouse and hamster COVID-19 models. [ABSTRACT FROM AUTHOR]