BBV152, a whole-virion inactivated SARS-CoV-2 vaccine (COVAXIN®, Bharat Biotech), was safe and immunogenic with high neutralizing antibodies titers, according to interim results of a phase 2 clinical trial published in The Lancet Infectious Diseases.
In this double-blind, randomized trial (ClinicalTrials.gov Identifier: NCT04471519) conducted at 9 hospitals across 9 states in India, researchers evaluated the safety and immunogenicity of 2 intramuscular doses of BBV152 vaccine formulated with an imidazoquinoline class molecule (TLR7/TLR8 agonist abbreviated as IMDG) adsorbed to aluminum hydroxide gel (Algel). Participants between the ages of 12 and 65 years were randomly assigned in a 1:1 ratio to receive either a 3-μg dose with Algel-IMDG or a 6-μg dose with Algel-IMDG on days 0 and 28. The primary outcomes were neutralizing antibody titers and seroconversion rates at day 56 (4 weeks after second dose).
Of the 380 participants enrolled in the study, 190 received 3-μg dose and 190 received 6-μg dose. In both groups, the majority were men (74% and 76%, respectively) and between the ages of 18 and 55 years (91% and 93%, respectively). At day 56, the retention rates were 97% in the 3-μg group and 93% in the 6-μg group.
At day 56, geometric mean titers (GMTs) analyzed with a plaque-reduction neutralization test (PRNT50) were significantly higher in the 6-μg group (197.0; 95% CI, 155.6-249.4) than the 3-μg group (100.9; 95% CI, 74.1-137.4; P =.0041) and comparable to convalescent serum collected from patients who had recovered from COVID-19 (P =.54). Similarly, GMTs analyzed with a microneutralization test (MNT50) were also significantly higher in the 6-μg vs 3-μg group (160.1 [95% CI, 135.8-188.8] vs 92.5 [95% CI, 77.7-110.2]).
At day 56, seroconversion occurred in 98.3% of participants in the 6-μg group and 92.9% in the 3-μg group based on PRNT50; and, 96.6% in the 6-μg groups and 88.0% in the 3-μg group based on MNT50.
Two weeks after the second dose (day 42), researchers observed that both doses had a T-helper 1 (Th1)-biased cell response with a significant increase in Th1-associated cytokines.
Local and systemic adverse reactions in both vaccine groups were minimal after 2 doses. The most common adverse events were injection site pain, headache, fatigue, and fever, which resolved within 24 hours. No serious adverse events were reported up to day 118.
Follow-up data of participants from the phase 1 trial at 3 months after their second dose, in which the 2 doses were administered 2 weeks apart rather than 4 weeks apart, showed that neutralizing antibody titers were similar to a panel of convalescent serum samples, as well as memory T-cells.
Findings from this study as well as the follow-up phase 1 trial shows that BBV152 has the “potential to provide durable humoral and cell-mediated immune responses,” noted the researchers. In addition, results from the phase 2 trial showed that the 6-μg dose has the ability to successfully neutralize the UK variant of SARS-CoV-2 known as B.1.1.7 or 20B/501Y.V1.
Limitations of this study included a small number of participants between the ages of 12 and 18 years, as well as 55 and 65 years. Researchers were unable to assess binding antibodies and cell mediated responses in convalescent serum because of the low quantity of those samples available. Lastly, the trial lacked ethnic, racial, and gender diversity.
BBV152, the 6-μg with Algel-IMDG formulation, has received emergency use authorization in India, and a phase 3 efficacy trial is currently in progress.
Disclosure: This clinical trial was supported and funded by Bharat Biotech International. Several study authors listed being employees of Bharat Biotech. Please see the original reference for a full list of authors’ disclosures.
Ella R, Reddy S, Harsh J, et al. 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. Lancet Infect Dis. Published online March 8, 2021. doi:10.1016/S1473-3099(21)00070-0