Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial
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Abstract
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SciScore for 10.1101/2020.07.31.20161216: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The trial protocol and the informed-consent form were approved by the ethics committee of the Jiangsu Provincial Center for Disease Control and Prevention (JSCDC).
Consent: Before enrollment, written informed consent was obtained from each participant.Randomization TRIAL DESIGN AND OVERSIGHT: This double-blind, randomized and placebo-controlled phase 2 clinical trial based on a seamless design was registered at clinicaltrials.gov (NCT04352608) and was conducted in Suining County. Jiangsu Province. China. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
… SciScore for 10.1101/2020.07.31.20161216: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The trial protocol and the informed-consent form were approved by the ethics committee of the Jiangsu Provincial Center for Disease Control and Prevention (JSCDC).
Consent: Before enrollment, written informed consent was obtained from each participant.Randomization TRIAL DESIGN AND OVERSIGHT: This double-blind, randomized and placebo-controlled phase 2 clinical trial based on a seamless design was registered at clinicaltrials.gov (NCT04352608) and was conducted in Suining County. Jiangsu Province. China. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources SARS-CoV-2 virus was propagated in Vero cells and harvested. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources Analyses were conducted by SAS 9.4 (SAS Institute, Cary, NC, USA). SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)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:Several limitations of this trial should be noted. Firstly, we only assessed the humoral immunity in phase 2 trial, and more evaluation focus on response of Th1 and Th2 is ongoing. Secondly, we only reported immune response data on healthy adults, and do not include data on more susceptible populations, such as elderly or with comorbidity; and also the immune persistence is not available yet, which need to be further studied. Thirdly, we didnt compare the neutralizing antibody titers induced by CoronaVac and convalescent COVID-19 patients in parallel, however, we conducted this detection of convalescent serum specimens with same procedure performed in this phase 2 trial. In conclusion, favorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages in this phase 2 clinical trial, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios. Currently, our first priority is to evaluate the protective efficacy of the 3 μg dosage under Day 0,14 schedule. Moreover, Day 0,28 schedule with 3 μg vaccine will also be adopted in our future phase 3 clinical trials.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04352608 Active, not recruiting Safety and Immunogenicity Study of Inactivated Vaccine for P… 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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Our take
In this study, available as a preprint and thus not yet peer reviewed, COVID-19 vaccines utilizing inactivated whole SARS-CoV-2 continue to show promise in clinical trial data reported to date, with good safety profiles and acceptable immunogenicity. The vaccine evaluated here – Sinovac’s CoronaVac – likely compares favorably with the virtually identical offering from Sinopharm, although the several limitations noted above hinder more definitive conclusions at this time.Substantial revision will likely be present in any peer-reviewed version of this article, so the evaluation here should be taken with caution. Furthermore, the phase 3 trials currently either planned or underway with this vaccine in Bangladesh, Brazil, and Indonesia should yield crucial additional information.
Study design
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Our take
In this study, available as a preprint and thus not yet peer reviewed, COVID-19 vaccines utilizing inactivated whole SARS-CoV-2 continue to show promise in clinical trial data reported to date, with good safety profiles and acceptable immunogenicity. The vaccine evaluated here – Sinovac’s CoronaVac – likely compares favorably with the virtually identical offering from Sinopharm, although the several limitations noted above hinder more definitive conclusions at this time.Substantial revision will likely be present in any peer-reviewed version of this article, so the evaluation here should be taken with caution. Furthermore, the phase 3 trials currently either planned or underway with this vaccine in Bangladesh, Brazil, and Indonesia should yield crucial additional information.
Study design
randomized-controlled-trial
Study population and setting
This study reports the findings from a phase 2 clinical trial evaluating the safety and immunogenicity of Sinovac’s CoronaVac COVID-19 vaccine, which consists of β-propiolactone inactivated whole SARS-CoV-2 with an aluminum hydroxide adjuvant. The trial was double-blinded, placebo-controlled, and involved 600 adults (ages 18-59) in Suining County, Jiangsu Province, China. Two doses (3 μg/mL or 6 μg/mL) were utilized in two schedules (injections on days 0 and 14, or days 0 and 28) in a ratio of 2:2:1 between the two vaccinated groups and the placebo group. Safety was assessed by self-reported adverse reactions, and immunogenicity was assessed by measuring total specific IgG against the receptor binding domain (RBD) and by measuring the neutralizing antibody (NAb) response.
Summary of main findings
Vaccination with CoronaVac was generally safe, with no serious adverse reactions reported, and immunogenic, with high NAb seroconversion rates (> 90%).
Study strengths
The study design is generally acceptable and the data indicate that, similarly to the inactivated vaccine in development by Sinopharm, Sinovac’s CoronaVac may have a superior profile to many other vaccine platforms currently in clinical trials.
Limitations
This study has numerous limitations. The safety assessment consisted of only self-reported adverse reactions; blood samples for laboratory analysis were not obtained, and no data were provided regarding some of the specific safety concerns with COVID-19 vaccination (e.g. antibody-dependent enhancement). Immunogenicity was assessed only in terms of humoral response, and the data are not presented clearly (e.g. seroconversion rates are only generically said to be ‘over 90%’). Additionally, the total IgG assay used only the RBD as the antigen, the NAb assay used (a ‘modified cytopathogenic effect’) differs from those employed by most other COVID-19 vaccine studies to date (which use plaque reduction neutralization tests) which makes cross-study comparisons difficult. Also the explanations provided for the improved immunogenicity seen with vaccine formula used in the phase 2 trial versus that used in phase 1 (i.e. a greater amount of spike protein per virion), are questionable and insufficient data are presented for this assessment. Regarding the phase 1 trial, references to ‘detailed information’ and a ‘coordinated submission’ of the phase 1 results are made, but we are unaware of any information available on the phase 1 results beyond Sinovac press reports and the phase 1 data confusingly scattered throughout this manuscript. Finally, numerous typographical errors (including grammatical/spelling mistakes and formatting irregularities), as well as a generally poor overall structure render this article difficult to read and reduce confidence in the data reported.
Value added
This study is the second to report clinical trial results assessing inactivated SARS-CoV-2 as a vaccine for COVID-19, and lends tentative additional support for this approach.
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