RESUMEN
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
RESUMEN
Analysing infection and mortality data for COVID-19 as a function of days for 54 countries across all continents, we show that there is a simple scaling behaviour connecting these two quantities for any given nation when the data is segmented over few ranges of dates covering the most rapid spread of the pandemic and the recovery, wherever achieved. This scaling is described by two parameters, one representing a shift along the time axis and the other is a normalisation factor, providing a reliable definition of the mortality rate for each country in a given period. The number of segments for any country required in our analyses turns out to be surprisingly few with as many as 16 out of 54 countries being described by a single segment and no country requiring more than three segments. Estimates of the shift and mortality for these 54 countries in different periods show large spreads ranging over 0-16 days and 0.45-19.96%, respectively. Shift and mortality are found to be inversely correlated. Analyses of number of tests carried out for detecting COVID-19 and the number of infections detected due to such tests suggest that an effective way to increase the shift, and therefore, decrease mortality, is to increase number of tests per infection detected. This points to the need of a dynamic management of testing that should accelerate with the rise of the pandemic; it also suggests a basis for adjusting variations in the testing patterns in different geographical locations within a given country.
