BackgroundWe present the data from an open-label study involved in the selection of optimum formulation of RBD-based protein sub-unit COVID-19 vaccine.MethodsThe 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.FindingsLow 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, nAb-titers and cellular immune-responses while maintaining the safety profile. Interestingly, binding and neutralizing antibody titers were persisted consistently till 6 months post second vaccine dose.InterpretationsCorbevax 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. The study was prospectively registered with clinical trial registry of India-CTRI/2021/06/034014 and CTRI/2020/11/029032.FundingBill & Melinda Gates Foundation, BIRAC-division of Department of Biotechnology, Govt of India, and the Coalition for Epidemic Preparedness Innovations funded the study.
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 current scenario of typhoid fever warrants early prevention with typhoid conjugate vaccines in susceptible populations to provide lifelong protection. We conducted a multicenter, single-blind, randomized, Phase 2/3 study to assess the immunogenicity and safety of Biological E’s Typhoid Vi-CRM
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conjugate vaccine (TyphiBEV
TM
) compared to Vi-TT conjugate vaccine manufactured by Bharat Biotech International Limited (Typbar-TCV; licensed comparator) in healthy infants, children, and adults from India. The study’s primary objective was to assess the non-inferiority of TyphiBEV
TM
in terms of the difference in the proportion of subjects seroconverted with a seroconversion threshold value of ≥2.0 µg/mL against Typbar-TCV. A total of 622 healthy subjects (311 each in both vaccine groups) were randomized and received the single dose of the study vaccine. The TyphiBEV
TM
group demonstrated noninferiority compared to the Typbar-TCV group at Day 42. The lower 2-sided 95% confidence interval limit of the group difference was −.34%, which met the non-inferiority criteria of ≥10.0%. The geometric mean concentration (24.79 µg/mL vs. 26.58 µg/mL) and proportion of subjects who achieved ≥4-fold increase in antiVi IgG antibody concentrations (96.95% vs. 97.64%) at Day 42 were comparable between the TyphiBEV
TM
and Typbar-TCV vaccine groups. No apparent difference was observed in the safety profile between both vaccine groups. All adverse events reported were mild or moderate in intensity in all age subsets. This data demonstrates that TyphiBEV
TM
is non-inferior to TypbarTCV in terms of immunogenicity, and the overall safety and reactogenicity in healthy infants, children, and adults studied from India was comparable.
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