Safety and immunogenicity of inactivated whole virion vaccine CoviVac against COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase I/II clinical trial
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Abstract
We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60.
Safety of the vaccine was assessed in 398 volunteers who received two doses of the vaccine (n=298) or placebo (n=100). The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AE), or other significant AE related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p<0.05).
Immunogenicity assessment was performed in 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening.
At Day 42 after the first immunization the seroconversion rate in participants who were seronegative at screening was 86.9% with average the geometric mean neutralizing antibody (nAB) titer of 1:20. Statistically significant (p<0.05) increase of IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the first immunization.
In participants who were seropositive at screening but had nAB titers below 1:256 the rate of 4-fold increase in nAB levels was 85.2%, while in the participants with nAB titers >1:256 the rate of 4-fold increase in nAB levels was below 45%. For the participants who were seropositive at screening the second immunization did not lead to a significant increase in nAB titers.
In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with 86.9% seroconversion rates in participants, who were seronegative at screening. In participants who were seropositive at screening and had nAB titers below 1:256, a single immunization lead to a 4-fold increase in nAB levels in 85.2% cases.
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SciScore for 10.1101/2022.02.08.22270658: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol (VKI-I/II-08/20) and its supplementary documentation were approved by the Ethics Committee of the Ministry of Health of the Russian Federation (No. 502 from September 21, 2020).
Consent: All participants were screened for eligibility on the basis of their health status, including their medical history, vital signs, physical examination and laboratory test results, and were enrolled after providing signed and dated informed consent forms.Sex as a biological variable not detected. Randomization Study design and participants: The study is a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity (Clinical … SciScore for 10.1101/2022.02.08.22270658: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study protocol (VKI-I/II-08/20) and its supplementary documentation were approved by the Ethics Committee of the Ministry of Health of the Russian Federation (No. 502 from September 21, 2020).
Consent: All participants were screened for eligibility on the basis of their health status, including their medical history, vital signs, physical examination and laboratory test results, and were enrolled after providing signed and dated informed consent forms.Sex as a biological variable not detected. Randomization Study design and participants: The study is a randomized, double-blind, placebo-controlled, multi-center clinical trial of the tolerability, safety, and immunogenicity (Clinical trials, phase I/II) of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in adult volunteers aged 18-60. Blinding The laboratory specialists were provided with the samples marked with coded numbers, and thus were also blinded. Power Analysis Statistical analysis: The sample size was determined based on the requirements of the national guidelines, and the distribution of the participants between Vaccine Group and Placebo Group was 3:1. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The participants of Stages 1 and 2 were also screened at enrolment for anti-SARS-CoV-2 IgM and IgG antibodies by ELISA. anti-SARS-CoV-2 IgMsuggested: (Bethyl Cat# E88-302, RRID:AB_2892019)IgG antibodies by ELISAsuggested: NoneSerum samples from randomly selected participants were additionally tested in ELISA for total antibodies against RBD with CoronaPass Total (Genetico, Russia) and for total antibodies to S protein trimer (Vector-Best, Russia) Vector-Best , Russiasuggested: NoneExperimental Models: Cell Lines Sentences Resources Neutralization test was performed using SARS-CoV-2 strain PIK35 in Vero cells as described previously (Kozlovskaya et al., 2021) Verosuggested: NoneSoftware and Algorithms Sentences Resources IgG antibodies to nucleocapsid protein (N) were detected using Architect SARS-CoV-2 IgG CMIA (Abbott Diagnostics, USA) Abbottsuggested: (Abbott, RRID:SCR_010477)Interferon-gamma (IFN-γ) production in response to stimulation with SARS-CoV-2 S-protein peptides was assessed using QuantiFERON SARS-CoV-2 QuantiFERONsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT05046548 Completed This is a Double-blind, Placebo-controlled, Randomized Study… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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