Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial

• Published in: The Lancet infectious diseases 2023-09, Vol.23 (9), p.1020-1030
• Main Authors: Wu, Jun-Dong, Li, Jing-Xin, Liu, Jian, Wang, Hao-Meng, Zhou, Guang-Hui, Li, Jin, Wu, Dou, Chen, Xiang, Feng, Yan, Qi, Xiao-Yuan, Wang, Xue, Gou, Jin-Bo, Ma, Tie-Liang, Yang, Xiao-Yun, Xu, Li-Feng, Wan, Peng, Zhu, Tao, Wang, Zhong-Fang, Zhu, Feng-Cai, Wang, Ying, Ma, Xiaomin
• Format: Article
• Language: English
• Subjects: Adults; Allergies; Antibodies; Chronic illnesses; Clinical trials; COVID-19; COVID-19 vaccines; Deactivation; Double-blind studies; Effectiveness; Homology; Immune response; Immunogenicity; Infections; Infectious diseases; mRNA; mRNA vaccines; Proteins; Safety; Seroconversion; Severe acute respiratory syndrome coronavirus 2; Side effects; Translation; Vaccines; Virions
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(23)00199-8

Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18–59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p