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Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial.
Lancet Infect Dis. 2021 05; 21(5):637-646.LI

Abstract

BACKGROUND

To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel).

METHODS

We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519).

FINDINGS

Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 μg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups.

INTERPRETATION

BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.

FUNDING

Bharat Biotech International.

Authors+Show Affiliations

Bharat Biotech, Hyderabad, India.Bharat Biotech, Hyderabad, India. Electronic address: kmohan@bharatbiotech.com.Bharat Biotech, Hyderabad, India.Bharat Biotech, Hyderabad, India.Bharat Biotech, Hyderabad, India.Bharat Biotech, Hyderabad, India.Bharat Biotech, Hyderabad, India.Indian Council of Medical Research-National Institute of Virology, Pune, India.Indian Council of Medical Research-National Institute of Virology, Pune, India.Indian Council of Medical Research-National Institute of Virology, Pune, India.Indian Council of Medical Research, New Delhi, India.Indian Council of Medical Research, New Delhi, India.Nizams Institute of Medical Sciences, Hyderabad, India.Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India.All India Institute of Medical Sciences, New Delhi, India.All India Institute of Medical Sciences, Patna, India.Redkar Hospital, Dargalim, India.Gillurkar Hospital, Nagpur, India.Prakhar Hospital, Kanpur, India.SRM Hospital and Research Centre, Kattankulathur, India.Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India.All India Institute of Medical Sciences, New Delhi, India.Bharat Biotech, Hyderabad, India.Indian Council of Medical Research, New Delhi, India.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33485468

Citation

Ella, Raches, et al. "Safety and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine, BBV152: a Double-blind, Randomised, Phase 1 Trial." The Lancet. Infectious Diseases, vol. 21, no. 5, 2021, pp. 637-646.
Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021;21(5):637-646.
Ella, R., Vadrevu, K. M., Jogdand, H., Prasad, S., Reddy, S., Sarangi, V., Ganneru, B., Sapkal, G., Yadav, P., Abraham, P., Panda, S., Gupta, N., Reddy, P., Verma, S., Kumar Rai, S., Singh, C., Redkar, S. V., Gillurkar, C. S., Kushwaha, J. S., ... Bhargava, B. (2021). Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. The Lancet. Infectious Diseases, 21(5), 637-646. https://doi.org/10.1016/S1473-3099(20)30942-7
Ella R, et al. Safety and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine, BBV152: a Double-blind, Randomised, Phase 1 Trial. Lancet Infect Dis. 2021;21(5):637-646. PubMed PMID: 33485468.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. AU - Ella,Raches, AU - Vadrevu,Krishna Mohan, AU - Jogdand,Harsh, AU - Prasad,Sai, AU - Reddy,Siddharth, AU - Sarangi,Vamshi, AU - Ganneru,Brunda, AU - Sapkal,Gajanan, AU - Yadav,Pragya, AU - Abraham,Priya, AU - Panda,Samiran, AU - Gupta,Nivedita, AU - Reddy,Prabhakar, AU - Verma,Savita, AU - Kumar Rai,Sanjay, AU - Singh,Chandramani, AU - Redkar,Sagar Vivek, AU - Gillurkar,Chandra Sekhar, AU - Kushwaha,Jitendra Singh, AU - Mohapatra,Satyajit, AU - Rao,Venkat, AU - Guleria,Randeep, AU - Ella,Krishna, AU - Bhargava,Balram, Y1 - 2021/01/21/ PY - 2020/11/21/received PY - 2020/11/28/revised PY - 2020/12/04/accepted PY - 2021/1/25/pubmed PY - 2021/5/4/medline PY - 2021/1/24/entrez SP - 637 EP - 646 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 21 IS - 5 N2 - BACKGROUND: To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). METHODS: We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). FINDINGS: Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 μg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. INTERPRETATION: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. FUNDING: Bharat Biotech International. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/33485468/Safety_and_immunogenicity_of_an_inactivated_SARS_CoV_2_vaccine_BBV152:_a_double_blind_randomised_phase_1_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(20)30942-7 DB - PRIME DP - Unbound Medicine ER -