Safety and immunogenicity clinical trial of an inactivated SARS-CoV-2 vaccine, BBV152 (a phase 2, double-blind, randomised controlled trial) and the persistence of immune responses from a phase 1 follow-up report
2020; Cold Spring Harbor Laboratory; Linguagem: Inglês
10.1101/2020.12.21.20248643
AutoresRaches Ella, Siddharth Reddy, Harsh Jogdand, Vamshi Sarangi, Brunda Ganneru, Sai Prasad, Dipankar Das, Dugyala Raju, Usha Praturi, Gajanan Sapkal, Pragya D. Yadav, Prabhakar Reddy, Savita Verma, Chandramani Singh, Sagar Vivek Redkar, Chandra Sekhar Gillurkar, Jitendra Singh Kushwaha, Satyajit Mohapatra, Amit Bhate, Sanjay Rai, Samiran Panda, Priya Abraham, Nivedita Gupta, Krishna M. Ella, Balram Bhargava, Krishna Mohan Vadrevu,
Tópico(s)Viral gastroenteritis research and epidemiology
ResumoAbstract 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). 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 µg and 6 µg with Algel-IMDG. Methods We 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 µg with Algel-IMDG and 6 µg 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 (PRNT 50 ). 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). Findings Among 921 participants screened between Sep 7-13, 2020, 380 participants were randomised to the safety and immunogenicity population. The PRNT 50 seroconversion rates of neutralising antibodies on day 56 were 92·9% (88·2, 96·2) and 98·3% (95·1, 99·6) in the 3 µg and 6 µg 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% (6·9, 13·2) and 10.3% (7·4, 13·8) in the 3 µg and 6 µg 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 73·5% (63·6, 81·9), 81·1% (71·4, 88·1), and 73·1% (62·9, 81·8) of individuals in the 3 µg with Algel-IMDG, 6 µg with Algel-IMDG, and 6 µg with Algel groups, respectively. Interpretation In 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 µg Algel-IMDG formulation was selected for the phase 3 efficacy trial. Funding This work was supported and funded by Bharat Biotech International Limited. Clinicaltrials.gov : NCT04471519
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