Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults

SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults. Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19–80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies. Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7–8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7–8 months after the third dose. https://rpcec.sld.cu/trials/RPCEC00000347 This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20). [Display omitted] •Heterologous schedule was well tolerated in a cohort of 810 adults aged 19–80 years•Specific IgG and neutralizing antibody responses were observed after vaccination•Neutralizing GMT versus D614G variant persisted after 7–8 months of vaccination•Serum samples of vaccinees neutralized VOCs Alpha, Beta, Delta, and Omicron Conjugate vaccine candidate SOBERANA 02 (recombinant receptor-binding domain [RBD] conjugated to tetanus toxoid) was previously evaluated in open-label phase I and IIa clinical trials. Here, Toledo-Romani et al. report the results of a double-blind, placebo-controlled phase IIb trial assessing immunogenicity and safety of SOBERANA 02 in a three-dose heterologous schedule with SOBERANA Plus (recombinant RBD dimer) in adults aged 19–80. The autho