Immunogenicity and safety of Biological Es CORBEVAX vaccine as a heterologous booster dose in adult volunteers previously vaccinated with two doses of either COVISHIELD or COVAXIN: A Prospective double-blind randomised phase III clinical study

BackgroundVaccines developed against Covid-19 infection were effective in controlling symptomatic infections and hospitalizations. However, waning immunity was reported within 6 months of primary vaccination series. Due to waning of SARS-CoV-2 specific primary immunity, protection towards emerging variants of concern (VoC) was low. To rejuvenate the immunogenicity of vaccines, a third or booster dose was highly recommended by many state governments. In this regard, several clinical studies were conducted to evaluate the homologous or heterologous booster dose effectiveness against VoCs and showed that heterologous immune boosting more effective in controlling breakthrough infections. In this study, we studied the safety and immunogenicity of Biological-Es CORBEVAX vaccine in adult population as a heterologous booster dose. MethodsThis is a prospective phase-3, randomised, double-blind, placebo-controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX vaccine as a heterologous booster dose administered to adult volunteers previously vaccinated with two doses of either COVISHIELD or COVAXIN at least 6 months ago. Subjects were RT-PCR negative to SARS-CoV-2 prior to enrolment. A total of 416 subjects between 18 to 80 years of age, were enrolled in to one of the two treatment (COVISHIELD or COVAXIN primed subjects) groups (n=208/group) for safety and immunogenicity assessment. Within each group (n=208), subjects were randomized to receive CORBEVAX vaccine or placebo in a 3:1 ratio. FindingsThe safety profile of CORBEVAX vaccine administered as booster dose is comparable to the placebo-control group. All the reported adverse events (AEs) were mild to moderate in their intensity. There was no grade 3 or serious or AEs of special interest (AESI) reported during the study period and all the reported AEs resolved without any sequelae. CORBEVAX booster dose administration resulted in significant increase in humoral immune response (nAb titers and Anti-RBD IgG concentration) that was much superior to the placebo in both COVISHIELD and COVAXIN recipient arms. Significant increase in nAb titers against Omicron VOC as well as cellular immune response was also observed post CORBEVAX booster dose administration. InterpretationsEnhancement of immune response coupled with excellent safety profile of the CORBEVAX booster dose demonstrates significant benefit of giving CORBEVAX heterologous booster dose to subjects that have received COVISHIELD or COVAXIN primary vaccination; as early as 6 months post second dose of primary vaccination. The study was prospectively registered with clinical trial registry of India-CTRI/2022/01/039366