Randomized Controlled Trial
Study population and setting
This paper describes the use of BBV152 (developed by Bharat Biotech), a whole virion inactivated SARS-CoV-2 vaccine. The vaccine formulation also uses a TLR 7/8 agonist called IMDG adsorbed to alum (Algel) as an adjuvant and to increase cell-mediated responses. The phase 1 trial tested a 3ug dose with Algel-IMDG, a 6ug dose with Algel-IMDG, 6ug with Algel, and Algel only, administered on days 0 and 14. The 3ug dose with Algel-IMDG and 6ug dose with Algel-IMDG formulations were selected for further testing in phase 2. 380 participants between the ages of 12 and 65 years were selected for phase 2, randomized 1:1 to receive either a 3ug dose with Algel-IMDG or a 6ug dose with Algel-IMDG on days 0 and 28. The trial took place in 9 hospitals across 9 states in India, with phase 2 participants enrolled between September 5 and 12, 2020. The primary outcomes were neutralizing antibody titers and seroconversion rates, with cell mediated responses being a secondary outcome. Safety was also assessed.
Summary of Main Findings
Neutralizing antibodies were increased by day 56 in both the 3 and 6ug dose groups, with levels significantly higher in the 6ug dose group. Levels of neutralizing antibodies in the 6ug dose group were also comparable to those found in convalescent serum. Seroconversion also occurred in 92.9% of participants in the 3ug dose group and 98.3% of participants in the 6ug dose group by day 56. A Th1-biased cell response was detected at day 42, with a significant increase in Th1-associated cytokines. The most common adverse events were injection site pain, followed by headache, fatigue, and fever. These occurred in only a small percentage of participants, were mostly mild, and resolved within 24 hours of onset. There was no significant difference in adverse events between the two dose groups, and no serious adverse events were reported. When following up with phase 1 participants 3 months after their second dose, participants still had detectable neutralizing antibody levels comparable to convalescent serum samples, as well as memory T-cells.
This study included a small number of young adults between the ages of 12 and 18 years, which is an age not included in many other trials. There was a diverse range of geographic locations across India included in the trial. The BBV152 vaccine was also successfully able to neutralize variant of concern B.1.1.7, also known as the UK variant. Additionally, the vaccine has the potential to provide a durable immune response based on the follow-up results from the phase 1 trial participants.
Binding antibodies and cell mediated responses in convalescent serum were unable to be assessed here due to the low quantity of those samples available. This trial lacked ethnic, racial, and gender diversity, with about 3/4 of participants being male. Finally, long-term follow-up data from the phase 2 participants may look different than the results from phase 1 participants due to different dosing schedules (days 0 and 28 as opposed to days 0 and 14).
First report of phase 2 and phase 1 follow-up results from the Indian BBV152 inactivated whole virion vaccine.