The efficacy and safety of an intranasal spray COVID-19 vaccine in a randomized double-blind placebo-controlled phase Ⅲ trial during Omicron period

Abstract The live-attenuated influenza virus vector-based intranasal vaccine (dNS1-RBD, Pneucolin®) is the world’s first COVID-19 mucosal vaccine to enter human trials, and has been issued for emergency use authorization in China. Here, we report safety and efficacy data from a multi-centre randomized, double-blind, placebo-controlled phase 3 clinical trial of Pneucolin® (two doses, 14 days apart) in adults (18 years and older) during the Omicron circulation. The result showed a favorable safety profile, with no difference in the incidence of adverse reactions between the vaccine and placebo groups. In the per-protocol set, for symptomatic COVID-19, the efficacies among total population, naïve participants, particiants with inactivated vacciantion history were 32.6% (95%CI 8.2 to 50.5), 55.2% (95%CI 13.8 to 76.7), 38.2% (95%CI -49.2 to 74.4) , and for symptomatic COVID-19 with three or more of the suspected symptoms, the efficacies were 42.3% (95%CI 15.7 to 60.5), 66.7% (95%CI 8.3 to 87.9) and 63.1% (95%CI -15.8 to 88.3) for the above mentioned 3 cohorts. An efficacy of 100.0% (95%CI -9.2 to 100.0) against hospitalized COVID-19 was observed in the whole enrolled population. We conclude that Pneucolin® is well-tolerated and can be an antibody-independent broad-spectrum effective tool to combat SARS-CoV-2 variants, as primary immunization or heterologous booster.