Immunogenic superiority and safety of Biological E CORBEVAX vaccine compared to COVISHIELD (ChAdOx1 nCoV-19) vaccine studied in a phase III, single blind, multicenter, randomized clinical trial

Abstract

Background: Optimum formulation of Biological Es CORBEVAX vaccine that contains protein sub unit of Receptor Binding Domain (RBD) from the spike protein of SARS-COV-2 formulated with aluminum hydroxide (Al3+) and CpG1018 as adjuvants was selected in phase-1 and 2 studies and proven to be safe, well tolerated and immunogenic in healthy adult population. In the current study, additional data was generated to determine immunogenic superiority of CORBEVAX vaccine over COVISHIELD vaccine and safety in larger and older population. Methods: This is a phase III prospective, single blinded, randomized, active controlled study (CTRI/2021/08/036074) conducted at 18 sites across India in healthy adults aged between 18-80 years. This study has two arms; immunogenicity arm and safety arm. Participants in immunogenicity arm were randomized equally to either CORBEVAX or COVISHIELD vaccination groups to determine the immunogenic superiority. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled. Findings: The safety profile of CORBEVAX vaccine was comparable to the comparator vaccine COVISHIELD in terms of overall AE rates, related AE rates and medically attended AEs. Majority of reported AEs were mild in nature, and overall CORBEVAX appeared to cause fewer local and systemic adverse reactions/events. Overall, two grade-3 serious AEs (Dengue fever and femur fracture) were reported and they are unrelated to study vaccine. Neutralizing Antibody titers, against both Ancestral and Delta strain, induced post two-dose vaccination regimen were higher in the CORBEVAX arm as compared to COVISHIELD and the analysis of GMT ratios demonstrated immunogenic superiority of CORBEVAX in comparison with COVISHIELD. Both CORBEVAX and COVISHIELD vaccines showed comparable seroconversion post vaccination when assessed against anti-RBD IgG response. The subjects in CORBEVAX cohort also exhibited higher Interferon-gamma secreting PBMCs post stimulation with SARS-COV-2 RBD peptides than the subjects in COVISHIELD cohort. Interpretations: Neutralizing antibody titers induced by CORBEVAX vaccine against Delta and Ancestral strains were protective, indicative of vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies. Safety findings revealed that CORBEVAX vaccine has excellent safety profile when tested in larger and older population.

The Lancet Commission on lessons for the future from the COVID-19 pandemic

“…430 As another example, the non-profit Texas Children's Hospital Center for Vaccine Development at Baylor College of Medicine, Texas, United States, worked with Biological E with no patents to produce and distribute a novel paediatric COVID-19 vaccine for emergency use in India, which was administered to more than 10 million adolescents in its first 10 days. 431,432 Alternative technologies, including recombinant protein COVID-19 vaccines, are not protected by patents and could have been made available early in the pandemic at very low cost or no cost to LMICs, alongside the patentprotected vaccines that use newer technologies. Some of the off-patent vaccines were produced at scale in LMICs by the Developing Country Vaccine Manufacturing Network (DCVMN).…”

“…430 As another example, the non-profit Texas Children's Hospital Center for Vaccine Development at Baylor College of Medicine, Texas, United States, worked with Biological E with no patents to produce and distribute a novel paediatric COVID-19 vaccine for emergency use in India, which was administered to more than 10 million adolescents in its first 10 days. 431 , 432 …”

Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response

“…The RBD is thought to transiently sample an "up" conformation compatible with Ace2 binding, which exposes neutralizing epitopes including some that may cross-protect against other coronaviruses (22)(23)(24)(25)(26). Consistent with these observations, the native RBD sequence is an effective vaccine (27,28). However, the RBD contacts other domains in the context of the full-length (FL)-spike protein, contains nonneutralizing epitopes, and may not stably present all neutralizing epitopes.…”

What the COVID-19 pandemic revealed about intellectual property

“…Corbevax is an unpatented vaccine that has been transferred to companies in lower-income countries. Developed at Texas Children's Hospital and Baylor College of Medicine without government or industry support, the vaccine cost only US$7 million to develop 25,26 and some studies suggest it is approximately as effective as mRNA vaccines 27,28 . The developers of the vaccine transfer know-how to companies interested in manufacturing it, with those manufacturers responsible for seeking regulatory approval.…”