Selection of Optimum Formulation of RBD-Based Protein Sub-Unit Covid19 Vaccine (Corbevax) Based on Safety and Immunogenicity in an Open-Label, Randomized Phase-1 and 2 Clinical Studies

Background: We present the data from an open-label study involved in the selection of optimum formulation of receptor binding domain (RBD)-based protein sub-unit COVID-19 vaccine.Methods: The randomized Phase-1/2 trial followed by a Phase-2 trial was carried out to assess safety and immunogenicity of different formulation of COVID-19 vaccine (Corbevax) and select an optimum formulation for a Phase 3 study. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled.Findings: Low incidence of adverse events were reported post vaccination of different Corbevax formulations and majority were mild in nature and no Grade-3 or serious adverse events were observed. All formulations in Phase-1/2 study showed similar profile of humoral and cellular immune response with higher response associated with increasing CpG1018 adjuvant content at same RBD protein content. Hence, high concentration of CpG1018 was tested in phase-2 study, which showed significant improvement in immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers and cellular immune-responses while maintaining the safety profile. Interestingly, binding and neutralizing antibody titers were persisted consistently till six months post second vaccine dose.Interpretations: Corbevax was well tolerated with no observed safety concerns. Neutralizing antibody titers were suggestive of high vaccine effectiveness compared with human convalescent plasma or protective thresholds observed during vaccine efficacy trials of other COVID-19 vaccines. Trial Registration Details: The study was prospectively registered with clinical trial registry of India- CTRI/2021/06/034014 and CTRI/2020/11/029032.Funding Information: The study was funded by grants from the Bill & Melinda Gates Foundation, BIRAC- a division of the Department of Biotechnology, Govt of India, and by the Coalition for Epidemic Preparedness Innovations.Declaration of Interests: ST, VP, KT, SG, VY, RM, MK and SKM are employees of Biological E Limited and they don’t have any stock options or incentives. All other participating authors declare no competing interests.Ethics Approval Statement: The Investigational Review Board or Ethics Committee at each study site approved the protocol. The study was conducted in accordance with the principles defined in the Declaration of Helsinki, International Conference on Harmonization and the local regulatory guidelines. Written informed consents were obtained from all healthy volunteers prior to the enrollment.