Safety and immunogenicity of an inactivated virus particle vaccine for SARS-CoV-2, BIV1-CovIran: findings from double-blind, randomised, placebo-controlled, phase I and II clinical trials among healthy adults.

Autor:	Mohraz M; Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran., Salehi M; Department of Infectious Diseases and Tropical Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Tabarsi P; Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Abbasi-Kangevari M; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Ghamari SH; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Ghasemi E; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Amini Pouya M; Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Rezaei N; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Ahmadi N; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Heidari K; Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran., Malekpour MR; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Nasiri M; Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran., Amirzargar AA; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Saeedi Moghaddam S; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Larijani B; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Hosseini H; Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran hmdhosseini@gmail.com.; Center for Research & Training in Skin Diseases & Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2022 Apr 08; Vol. 12 (4), pp. e056872. Date of Electronic Publication: 2022 Apr 08.
DOI:	10.1136/bmjopen-2021-056872
Abstrakt:	Objective: Assessing safety and immunogenicity of an inactivated whole virus particle vaccine. Design: Single-centre, double-blind, randomised, placebo-controlled, phase I (stage I: 18-50, stage II: 51-75 years), phase II (18-75 years) clinical trials. Setting: 29 December 2020 to 22 April 2021. Participants: Stage I-phase I: 56 participants; stage II-phase I: 32; phase II: 280. Intervention: During stage I, participants randomly (3:3:1) received 3 µg, 5 µg vaccine or placebo in a 14-day interval. Participants in stage II received two shots of 5 µg vaccine or placebo (3:1). In phase II, participants received 5 µg vaccine or placebo (4:1) in a 28-day interval. Primary and Secondary Outcome Measures: Safety assessment and immunogenicity assessment via antibody response and conventional virus neutralisation test (cVNT). Results: All adverse events (AEs) were mild or moderate and transient in both phase I and phase II, and no AEs of special interest were reported. The seroconversion-rate of neutralising, antireceptor binding-domain (RBD) and anti-spike-glycoprotein (anti-S) antibodies 14-days after second dose of 5 µg vaccine in stage I was 70.8% (95% CI 48.9% to 87.4%), 87.5% (95% CI 67.6% to 97.3%), 91.7% (95% CI 73.0% to 99.0%). The antibody titres increased more among 5 µg than 3 µg. The corresponding rates for 3 µg vaccine were 45.8% (95% CI 25.6% to 67.2%), 54.2% (95% CI 32.8% to 74.5%) and 70.8% (95% CI 48.9% to 87.4%), respectively. In stage II, 100% (95% CI 84.6% to 100%), 86.4% (95% CI 65.1% to 97.1%) and 86.4% (95% CI 65.1% to 97.1%) of participants seroconverted for neutralising, anti-RBD and anti-S antibodies. In phase II, the seroconversion rate of neutralising-antibody was 82.8% (95% CI 77.0% to 87.6%), anti-RBD 77.0% (95% CI 70.7% to 82.6%) and anti-S 79.9% (95% CI 73.8% to 85.1%) on day 42. In the cVNT, the sera at 1/64 times dilution would neutralise SARS-CoV-2 among 91.7%, 77.3% and 82.5% of vaccinated participants in phase I-stage I, phase I-stage II and phase II clinical trials, respectively. Conclusions: These results support further evaluation of this inactivated whole virus particle vaccine. Trial Registration Numbers: IRCT20201202049567N1 and IRCT20201202049567N2 for phase I and IRCT20201202049567N3 for phase II. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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