PMID- 35396297 OWN - NLM STAT- MEDLINE DCOM- 20220412 LR - 20221107 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 12 IP - 4 DP - 2022 Apr 8 TI - 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. PG - e056872 LID - 10.1136/bmjopen-2021-056872 [doi] LID - e056872 AB - 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 microg, 5 microg vaccine or placebo in a 14-day interval. Participants in stage II received two shots of 5 microg vaccine or placebo (3:1). In phase II, participants received 5 microg 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 microg 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 microg than 3 microg. The corresponding rates for 3 microg 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. CI - (c) 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. FAU - Mohraz, Minoo AU - Mohraz M AD - Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran. FAU - Salehi, Mohammadreza AU - Salehi M AD - Department of Infectious Diseases and Tropical Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. FAU - Tabarsi, Payam AU - Tabarsi P AD - Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Abbasi-Kangevari, Mohsen AU - Abbasi-Kangevari M AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Ghamari, Seyyed-Hadi AU - Ghamari SH AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Ghasemi, Erfan AU - Ghasemi E AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Amini Pouya, Maryam AU - Amini Pouya M AD - Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. FAU - Rezaei, Negar AU - Rezaei N AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Ahmadi, Naser AU - Ahmadi N AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Heidari, Kazem AU - Heidari K AD - Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Malekpour, Mohammad-Reza AU - Malekpour MR AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Nasiri, Mojtaba AU - Nasiri M AD - Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Amirzargar, Ali Akbar AU - Amirzargar AA AD - Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Saeedi Moghaddam, Sahar AU - Saeedi Moghaddam S AD - Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Larijani, Bagher AU - Larijani B AD - Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hosseini, Hamed AU - Hosseini H AUID- ORCID: 0000-0003-2368-6749 AD - Clinical Trial Center (CTC), Tehran University of Medical Sciences, Tehran, Iran hmdhosseini@gmail.com. AD - Center for Research & Training in Skin Diseases & Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20220408 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (Vaccines, Inactivated) SB - IM EIN - BMJ Open. 2022 Nov 7;12(11):e056872corr1. PMID: 36344009 MH - Adolescent MH - Adult MH - Aged MH - Antibodies, Viral MH - *COVID-19/prevention & control MH - *COVID-19 Vaccines/adverse effects MH - Double-Blind Method MH - Humans MH - Middle Aged MH - SARS-CoV-2 MH - Vaccines, Inactivated/adverse effects MH - Virion MH - Young Adult PMC - PMC8995575 OTO - NOTNLM OT - COVID-19 OT - adverse events OT - epidemiology OT - immunology OT - infectious diseases OT - microbiology COIS- Competing interests: None declared. EDAT- 2022/04/10 06:00 MHDA- 2022/04/13 06:00 PMCR- 2022/04/08 CRDT- 2022/04/09 05:18 PHST- 2022/04/09 05:18 [entrez] PHST- 2022/04/10 06:00 [pubmed] PHST- 2022/04/13 06:00 [medline] PHST- 2022/04/08 00:00 [pmc-release] AID - bmjopen-2021-056872 [pii] AID - 10.1136/bmjopen-2021-056872 [doi] PST - epublish SO - BMJ Open. 2022 Apr 8;12(4):e056872. doi: 10.1136/bmjopen-2021-056872.