Intranasal immunization expressing S1 antigen can confer functionally sterile protection against an intranasal SARS-CoV-2 challenge in mice

Currently approved COVID-19 vaccines have shown significant protective efficacy against disease onset and progression after SARS-CoV-2 infection. However, systemic immune responses induced by intramuscular vaccination have limited impact on protection of viral transmission. Intranasal vaccination is an important strategy for induction of mucosal immune responses for protection of viral transmission. Here, we investigated the potential of intranasal immunization expressing a SARS-CoV-2 spike (S) antigen to prevent SARS-CoV-2 infection in a mice model. Intranasal immunization with a Sendai virus vector expressing SARS-CoV-2 S1 domain fused with the trimerization domain of T4 fibritin induced neutralizing antibodies detected not only in plasma but also in bronchoalveolar lavage fluid (BALF) in BALB/c mice. After an intranasal challenge with a mouse-adapted SARS-CoV-2 strain QHmusX, all the unimmunized mice (n = 9) showed significant body weight loss and high viral load in BALF. In contrast, the intranasally-immunized mice (n = 8) had no detectable viral sgRNA nor infectious viruses in BALF except for one mouse with marginal level of sgRNA, showing no body weight loss. This study indicates that intranasal immunization expressing S1 antigen can confer functionally sterile protection against SARS-CoV-2 infection.