Immunogenicity and Safety of a 3-Dose Regimen of a SARS-CoV-2 Inactivated Vaccine in Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
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Abstract
Background
Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic needs effective vaccines.
Methods
In a phase 2 randomized, double-blind, placebo-controlled trial, 500 adults aged 18–59 years or ≥60 years were randomized in 2:2:1 ratio to receive 3 doses of 5 μg or 10 μg of a SARS-CoV-2 inactivated vaccine, or placebo separated by 28 days. Adverse events (AEs) were recorded through day 28 after each dosing. Live virus or pseudovirus neutralizing antibodies, and receptor binding domain immunoglobulin G (RBD-IgG) antibody were tested after the second and third doses.
Results
Two doses of the vaccine elicited geometric mean titers (GMTs) of 102–119, 170–176, and 1449–1617 for the 3 antibodies in younger adults. Pseudovirus neutralizing and RBD-IgG GMTs were similar between older and younger adults. The third dose slightly (<1.5 fold) increased GMTs. Seroconversion percentages were 94% or more after 2 doses, which were generally similar after 3 doses. The predominant AEs were injection-site pain. All the AEs were grade 1 or 2 in intensity. No serious AE was deemed related to study vaccination.
Conclusions
Two doses of this vaccine induced robust immune response and had good safety profile. A third dose given 28 days after the second dose elicited limited boosting antibody response.
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SciScore for 10.1101/2021.04.07.21253850: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The protocols and informed consents were approved by the institutional review board of JPCDC.
Consent: Written informed consent from all participants was obtained before screening for eligibility.Randomization Study design and participants: Both the phase 1 and phase 2 trials of KCONVAC were randomized, double-blind, and placebo-controlled studies and conducted in succession by Jiangsu Provincial Center for Disease Control and Prevention (JPCDC) beginning from Oct 2020. Blinding The experimental vaccines and placebo were blindly labelled with a randomisation number on each vial as the only identifiers. Power Analysis Statistical analysis: The sample size for … SciScore for 10.1101/2021.04.07.21253850: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The protocols and informed consents were approved by the institutional review board of JPCDC.
Consent: Written informed consent from all participants was obtained before screening for eligibility.Randomization Study design and participants: Both the phase 1 and phase 2 trials of KCONVAC were randomized, double-blind, and placebo-controlled studies and conducted in succession by Jiangsu Provincial Center for Disease Control and Prevention (JPCDC) beginning from Oct 2020. Blinding The experimental vaccines and placebo were blindly labelled with a randomisation number on each vial as the only identifiers. Power Analysis Statistical analysis: The sample size for the phase 1 trial was not determined on the basis of statistical power calculations but in line with the guidance issued by NMPA for phase 1 vaccine trial. Sex as a biological variable Pregnant or breastfeeding women were excluded. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody level of RBD-IgG subtypes including IgG1, IgG2, IgG3, IgG4 and antibody response to nucleoprotein of SARS-CoV-2 were determined by ELISA on Day 0, Day 14, Day 28 and Day 42. IgG2suggested: (George Fu Gao; Chinese Academy of Sciences; Beijing; China Cat# Z3L1, RRID:AB_2725798)IgG3, IgG4suggested: (George Fu Gao; Chinese Academy of Sciences; Beijing; China Cat# Z3L1, RRID:AB_2725798)Experimental Models: Cell Lines Sentences Resources The SARS-CoV-2 virus strain CQ01 was inoculated in Vero cell for cultivation. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Results 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: We detected the following sentences addressing limitations in the study:One limitation for this preliminary analysis is that we don’t include the safety and immunogenicity data of KCONVAC in elder adults who are at higher risk to COVID-19. These population are included in our protocol and will be the target in our ongoing studies. The second limitation is that the study duration of the trials is relative short, i.e., 28 days post the second dose. Therefore, long-term safety profile and antibody persistence are not in the scope of this preliminary analysis. Our ongoing studies and the upcoming phase 3 efficacy trial will be able to include these objectives. The third limitation is that we used ELISA instead of ELISpot to test the cytokines other than IFNγ and collected blood samples only once between the first and second doses. Therefore we could not get an overall profile of the cell response. The reason for using ELISA and this sampling schedule was that we intended to observe the safety only through the serum cytokines, and considered that inactivated virus vaccine might show weak cellular response. In conclusion, our two trials demonstrate that KCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04758273 Active, not recruiting A Safety and Immunogenicity Study of Inactivated SARS-CoV-2 … NCT04756323 Active, not recruiting A Study to Evaluate Safety and Immunogenicity of Inactivated… Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
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