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
© 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..
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.
| Errataetall: |
ErratumIn: BMJ Open. 2022 Nov 7;12(11):e056872corr1. - PMID 36344009 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
BMJ open - 12(2022), 4 vom: 08. Apr., Seite e056872 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mohraz, Minoo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.04.2022 Date Revised 07.11.2022 published: Electronic ErratumIn: BMJ Open. 2022 Nov 7;12(11):e056872corr1. - PMID 36344009 Citation Status MEDLINE |
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| doi: |
10.1136/bmjopen-2021-056872 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Safety and immunogenicity of an inactivated virus particle vaccine for SARS-CoV-2, BIV1-CovIran |b findings from double-blind, randomised, placebo-controlled, phase I and II clinical trials among healthy adults |
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| 500 | |a published: Electronic | ||
| 500 | |a ErratumIn: BMJ Open. 2022 Nov 7;12(11):e056872corr1. - PMID 36344009 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 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. | ||
| 520 | |a OBJECTIVE: Assessing safety and immunogenicity of an inactivated whole virus particle vaccine | ||
| 520 | |a 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 | ||
| 520 | |a SETTING: 29 December 2020 to 22 April 2021 | ||
| 520 | |a PARTICIPANTS: Stage I-phase I: 56 participants; stage II-phase I: 32; phase II: 280 | ||
| 520 | |a 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 | ||
| 520 | |a PRIMARY AND SECONDARY OUTCOME MEASURES: Safety assessment and immunogenicity assessment via antibody response and conventional virus neutralisation test (cVNT) | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: These results support further evaluation of this inactivated whole virus particle vaccine | ||
| 520 | |a TRIAL REGISTRATION NUMBERS: IRCT20201202049567N1 and IRCT20201202049567N2 for phase I and IRCT20201202049567N3 for phase II | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
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| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a adverse events | |
| 650 | 4 | |a epidemiology | |
| 650 | 4 | |a immunology | |
| 650 | 4 | |a infectious diseases | |
| 650 | 4 | |a microbiology | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Vaccines, Inactivated |2 NLM | |
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| 700 | 1 | |a Abbasi-Kangevari, Mohsen |e verfasserin |4 aut | |
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| 700 | 1 | |a Amini Pouya, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Rezaei, Negar |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmadi, Naser |e verfasserin |4 aut | |
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| 700 | 1 | |a Hosseini, Hamed |e verfasserin |4 aut | |
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