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 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.
Keywords: beta-coronavirus; boost-target; golden hamsters; immunoglobulin A; in vivo Ad5 transduction; intranasal vaccination; lentiviral vectors; lung inflammation; mucosal immunity; neutralizing antibodies; respiratory tracts.
【저자키워드】 Neutralizing antibodies, mucosal immunity, immunoglobulin A, intranasal vaccination, Lung inflammation, beta-coronavirus, boost-target, golden hamsters, in vivo Ad5 transduction, lentiviral vectors, respiratory tracts., 【초록키워드】 COVID-19, coronavirus disease, neutralizing antibody, SARS-CoV-2, Efficacy, Vaccine, immune response, vaccination, hamsters, lung, Prophylactic, immunization, serum, Neutralizing activity, Immunoglobulin, mice, vaccine candidate, Neutralizing, glycoprotein, adenoviral vector, respiratory tract, in vivo, expression, platform, SARS-CoV-2 replication, intranasal, boost, Evidence, mucosal, Injury, Deleterious, systemic, lung viral load, respiratory tracts, local inflammation, Effect, approach, decrease, receptor hACE2, log, develop, inhibit, reduce, the Spike, lentiviral, Ad5, respiratory tract cell, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, vaccination, animal model, PROTECT, lentiviral,