Safety and Immunogenicity of a SARS-CoV-2 Inactivated Vaccine Administered Simultaneously with an Inactivated Quadrivalent Influenza Vaccine: A Randomized, Open-Label, Controlled Study in Healthy Adults Aged 18 to 59 Years in China

Abstract

Background: Studies are needed to provide evidence for the immunization strategy of the COVID-19 vaccine simultaneously administered with the influenza vaccine. \n \nMethods: A randomised, open-label, controlled, phase 4 clinical trial was conducted in Zhejiang Province, east of China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive one dose of inactivated quadrivalent influenza vaccine (IIV4) either simultaneously with the first (SI1 subgroup, Day 0) or the second (SI2 subgroup, Day 28) dose of CoronaVac, or 14 days after the first dose of CoronaVac (SE group). The primary endpoint of the study was the non-inferiority in seroconversion rate of antibody against SARS-Cov-2 between participants who received two vaccines simultaneously and those who followed the separate vaccination schedule (clinicaltrials.gov number, NCT04801888). \n \nFindings: Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the SI1, SI2, and SE groups, respectively. With the noninferiority margin set at 10%, the seroconversion of antibodies against SARS-CoV-2 in the SI group (93.11% [89.04, 96.01]) was not inferior to that in the SE group (95.15% [91.50, 97.56]) in the per-protocol set. Overall, the geometric mean titer (GMT) in the SE group was higher than that in the SI group with statistical significance (38.06 vs. 27.54, P=0.0001). Within the SI group, the GMT was significantly higher in the SI1 subgroup than that in the SI2 subgroup (32.61 vs 23.26, P=0.0153). The occurrences of vaccine related adverse reactions were comparable among different vaccination groups (16.67% vs. 19.17% and 20.00%, P=0.7568). \n \nInterpretation: Simultaneous administration of both SARS-Cov-2 inactivated vaccine and seasonal influenza vaccine would be feasible. Further studies are needed to explain the unexpected decrease of immune response against SARS-CoV-2 following the regimen that IIV4 simultaneously administered with the 2 nd dose of the SARS-CoV-2 inactivated vaccine. \n \nTrial Registration: This study was registered at: (clinicaltrials.gov number, NCT04801888). \n \nFunding: This study was funded by the Vaccine Clinical Evaluation Platform Construction Project under China National Science and Technology Major Projects [2018ZX09734004] and The Key Research and Development Program of Zhejiang Province (2021C03200). \n \nDeclaration of Interest: GZ, XD and ZW are employees of Sinovac Biotech CO., Ltd. All other authors declare no competing interests. \n \nEthical Approval: The study protocol and informed consent form were approved by the ethics committee of the Zhejiang Provincial Center for Disease Control and Prevention (ZJCDC).