Immunogenicity and safety of Biological E's CORBEVAX™ vaccine as a heterologous booster dose in adult volunteers previously vaccinated with two doses of either COVISHIELD™ or COVAXIN: A prospective double-blind randomized phase III clinical study.

Objectives: Vaccines against COVID-19 significantly reduced symptomatic disease and hospitalization. However, waning and diminished protection against emerging variants of concern (VoCs) have warranted booster doses. Clinical studies comparing homologous and heterologous boosters demonstrate enhanced immunogenicity and breakthrough-infection control with heterologous regimens. In this context, we evaluated the safety and immunogenicity of a single heterologous CORBEVAX™ booster in adults in a prospective phase III, randomized, double-blind, placebo-controlled trial. Methods: Adults (18-80 years) previously primed ≥6 months earlier with two doses of COVISHIELD™ or COVAXIN™ were randomized 3:1 within each prime group to receive CORBEVAX™ or placebo. Study endpoints included safety, reactogenicity, tolerability, and humoral/cellular immunogenicity. Results: A total of 416 participants (208 per prime group) were enrolled. Post-CORBEVAX™ booster, we observed enhanced humoral responses-significantly increased neutralizing-antibody titers and anti-receptor-binding domain immunoglobulin G-and a T helper 1-skewed cellular response with increased interferon-gamma secretion. A superior post-booster neutralization response against the Omicron VoC was also observed. Adverse events were primarily mild-to-moderate (no adverse events of special interest) with a booster safety profile comparable to placebo. One serious adverse event occurred and was deemed unrelated to the booster. Conclusions: In conclusion, heterologous boosting with CORBEVAX™ substantially enhanced humoral and cellular immunity against SARS-CoV-2 VoCs while being well tolerated.