Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial

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 (IMDG) adsorbed to alum (Algel). We previously reported findings from a doubleblind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 µg and 6 µg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28.Methods We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12-65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 µg with Algel-IMDG or 6 µg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT 50 ) and the microneutralisation test (MNT 50 ). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at ClinicalTrials.gov, NCT04471519. FindingsBetween Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 µg with Algel-IMDG group (n=190) or 6 µg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT 50 ) at day 56 were significantly higher in the 6 µg with Algel-IMDG group (197•0 [95% CI 155•6-249•4]) than the 3 µg with Algel-IMDG group (100•9 [74•1-137•4]; p=0•0041). Seroconversion based on PRNT 50 at day 56 was reported in 171 (92•9% [95% CI 88•2-96•2] of 184 participants in the 3 µg with Algel-IMDG group and 174 (98•3% [95•1-99•6]) of 177 participants in the 6 µg with Algel-IMDG group. GMTs (MNT 50 ) at day 56 were 92•5 (95% CI 77•7-11...

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

“…32 ). Using the observed neutralization level (a mean of 79.2% of the convalescent titer in that study 33 (Supplementary Table 1), the predicted efficacy of the new vaccine was 79.6% (95% predictive interval: 76.2-83.0%), which is in very close agreement with the reported efficacy of 80.6% (ref. 32 ) and suggests good predictive value of the model (Fig.…”

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination

“…In the Phase 2 clinical trial, 380 participants were enrolled. 110 This study showed that BBV152-Covaxin has elicited high levels of neutralizing antibodies that remained elevated in all participants 3 months after the second vaccination. No serious adverse events were reported in this study.…”

Delivery Routes for COVID-19 Vaccines

“…Traditionally, vaccines are either attenuated or inactivated pathogens or protein subunits from the pathogen. As early as 1880, attenuated pathogen vaccines were developed by Pasteur [1], and attenuated virus vaccines now prevent measles, mumps, and rubella [41]. However, attenuating strains takes years, so this type of vaccine cannot be used to tackle the current pandemic, and there are also safety concerns.…”

“…BBV152 is effective in trafficking antigens to the draining lymph node without systemic circulation and has been demonstrated to be immunogenic, welltolerated, and safe in mice, rats, Syrian hamsters, and nonhuman primates [59][60][61]. A phase 2 clinical trial was successful and BBV152 is now being evaluated in a phase 3 clinical trial (NCT04641481) (Figure 2A) [41]. Inactivated vaccines are generated by chemical or heat stress.…”