ABSTRACT
Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
ABSTRACT
BackgroundBBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 {micro}g or 6 {micro}g) formulated with a Toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG). Earlier, we reported findings from a phase 1 (vaccination regimen on days 0 and 14) randomised, double-blind trial on the safety and immunogenicity of three different formulations of BBV152 and one control arm containing Algel (without antigen). Two formulations were selected for the phase 2 (days 0 and 28) study. Here, we report interim findings of a controlled, randomised, double-blind trial on the immunogenicity and safety of BBV152: 3 {micro}g and 6 {micro}g with Algel-IMDG. MethodsWe conducted a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152. A total of 380 healthy children and adults were randomised to receive two vaccine formulations (n=190 each) with 3 {micro}g with Algel-IMDG and 6 {micro}g with Algel-IMDG. Two intramuscular doses of vaccines were administered (four weeks apart). Participants, investigators, and laboratory staff were blinded to the treatment allocation. The primary outcome was seroconversion ([≥]4-fold above baseline) based on wild-type virus neutralisation (PRNT50). Secondary outcomes were reactogenicity and safety. Cell-mediated responses were evaluated. A follow-up blood draw was collected from phase 1 participants at day 104 (three months after the second dose). FindingsAmong 921 participants screened between Sep 7-13, 2020, 380 participants were randomised to the safety and immunogenicity population. The PRNT50 seroconversion rates of neutralising antibodies on day 56 were 92{middle dot}9% (88{middle dot}2, 96{middle dot}2) and 98{middle dot}3% (95{middle dot}1, 99{middle dot}6) in the 3 {micro}g and 6 {micro}g with Algel-IMDG groups, respectively. Higher neutralising titres (2-fold) were observed in the phase 2 study than in the phase 1 study (p<0.05). Both vaccine groups elicited more Th1 cytokines than Th2 cytokines. After two doses, the proportion (95% CI) of solicited local and systemic adverse reactions were 9.7% (6{middle dot}9, 13{middle dot}2) and 10.3% (7{middle dot}4, 13{middle dot}8) in the 3 {micro}g and 6 {micro}g with Algel-IMDG groups, respectively. No significant difference was observed between the groups. No serious adverse events were reported in this study. Phase 1 follow-up immunological samples at day 104 showed seroconversion in 73{middle dot}5% (63{middle dot}6, 81{middle dot}9), 81{middle dot}1% (71{middle dot}4, 88{middle dot}1), and 73{middle dot}1% (62{middle dot}9, 81{middle dot}8) of individuals in the 3 {micro}g with Algel-IMDG, 6 {micro}g with Algel-IMDG, and 6 {micro}g with Algel groups, respectively. InterpretationIn the phase 1 trial, BBV152 produced high levels of neutralising antibodies that remained elevated in all participants three months after the second vaccination. In the phase 2 trial, BBV152 led to tolerable safety outcomes and enhanced humoral and cell-mediated immune responses. The safety profile of BBV152 is noticeably lower than the rates for other SARS-CoV-2 vaccine platform candidates. The 6 {micro}g Algel-IMDG formulation was selected for the phase 3 efficacy trial. FundingThis work was supported and funded by Bharat Biotech International Limited. Clinicaltrials.gov: NCT04471519
ABSTRACT
Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a Toll-Like Receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or 6 μg with alum (Algel).Methods: We conducted a double-blind, randomised, multicentre, controlled phase 1 clinical trial to evaluate the safety and immunogenicity of BBV152. A total of 375 healthy adults Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation were randomised equally to receive three vaccine formulations (n=100 each) prepared with 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel, and an Algel only control arm (n=75). Two intramuscular doses of vaccines were administered (twoweeks apart). Primary outcomes were reactogenicity and safety. Secondary outcome was seroconversion (≥4-fold above baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot.Findings: Among 827 participants screened between July 13 and July 30, 2020, 375 participants were randomised. After both doses, the proportion (95%CI) of solicited local and systemic adverse reactions were 17% (10·5, 26·1), 21% (13·8, 30·5), 14% (8·1, 22·7), and 10% (6·9, 23·6) in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, 6 μg with Algel, and control groups, respectively . The most common solicited adverse events were injection site pain, headache, and fatigue. All solicited adverse events were mild (43, 69·3%) or moderate (19, 30·7%) and were more frequent after the first dose. One serious adverse event was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with AlgelIMDG, 6 μg with Algel-IMDG and 6 μg with Algel groups, respectively. CD4 + and CD8 + T cell responses were detected in a subset from both Algel-IMDG groups.Interpretations: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.Trial Registration Number: Clinicaltrials.gov : NCT04471519 Funding: This work was supported and funded by Bharat Biotech International Limited. Conflict of Interest: This work was supported and funded by Bharat Biotech International Limited. All authors are employees of one of the above-mentioned organisations, with no stock options or incentives. Co-author- K.E is the Chairman and Managing Director of Bharat Biotech.Ethical Approval: The trial was conducted across 11 sites in 9 states in India. The trial was approved by the National Regulatory Authority (India) and the respective Ethics Committees and was conducted in compliance with all International Council for Harmonization 114 (ICH) Good Clinical Practice guidelines.