Short-term effectiveness of single-dose intranasal spray COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron infection in healthcare workers: a prospective cohort study

Background The pivotal phase 3 efficacy clinical trial has demonstrated that a two-dose regimen of dNS1-RBD (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) is well-tolerated and provides wide protection against SARS-CoV-2 infection. However, the effectiveness of a single-dose regimen is still unknown. We aimed to estimate the effectiveness of one-dose of dNS1-RBD against symptomatic Omicron infections in real-world conditions.Methods This prospective cohort study was conducted during an Omicron outbreak among healthcare workers in Xiamen, China, from December 22, 2022 to January 16, 2023. Participants chose to receive single-dose of dNS1-RBD or remain unvaccinated based on personal preference. Healthcare workers daily validated their SARS-CoV-2 infection status, using either RT-PCR or rapid antigen test. A survey questionnaire was conducted to gather information on acute symptoms from individuals infected with SARS-CoV-2. The primary outcome was the symptomatic SARS-CoV-2 infections after enrollment in the dNS1-RBD recipients or the control group among all participants and by prior COVID-19 vaccination status.Findings On December 22, 2022, a total of 1391 eligible participants without a history of prior SARS-CoV-2 infection were enrolled. Among them, 550 received single-dose of dNS1-RBD, while 841 remained unvaccinated. In the total cohort, the range of follow-up time was 1 similar to 26 days. During the study period, a total of 880 symptomatic SARS-CoV-2 infections were identified in the total cohort. The adjusted vaccine effectiveness against symptomatic SARS-CoV-2 infections and the infections requiring medical attention were 19.0% (95% CI: 6.7, 29.7, P = 0.004) and 59.4% (95% CI: 25.1, 78.0, P = 0.004) in the total cohort, 11.6% (95% CI: -2.4, 23.7, P = 0.100) and 55.3% (95% CI: 15.3, 76.4, P = 0.014) in the participants with inactivated COVID-19 vaccination history, as well as 87.0% (95% CI: 72.6, 93.9, P < 0.001) and 84.2% (95% CI: -41.8, 98.2, P = 0.099) in the na & iuml;ve participants, respectively.Interpretation When administered as a booster to individuals with a history of inactivated COVID-19 vaccination, a single-dose of dNS1-RBD provides protection against infections requiring medical attention at least in the short-term after vaccination. The data also showed that a single-dose of dNS1-RBD is protective against symptomatic SARS-CoV-2 infections as a primary immunization for individuals without prior exposure, but due to the limited sample size of na & iuml;ve participants, further research with a larger sample size is needed to make a solid conclusion.