The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18–59 years: A phase I randomized, double-blinded, controlled trial
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Abstract
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Our take
The study, available as a preprint and thus not yet peer reviewed, showed that using an inactivated whole SARS-CO-V2 virus vaccine is safe with no major reactions detected in the participants. This is a new strategy for vaccine development against COVID-19, and could be a backup plan if the approach targeting viral spike protein strategy that is being used in most other vaccine development fails. The study also suggested that this inactivated vaccine induces an immune response against several viral antigens. However, the efficacy of this vaccine needs to be tested in phases II and III trials.
Study design
randomized-controlled-trial
Study population and setting
This is a phase I randomized, double blinded, placebo-controlled trial of inactivated SARS-CO-V2 vaccine in adults aged between 18-59 …
Our take
The study, available as a preprint and thus not yet peer reviewed, showed that using an inactivated whole SARS-CO-V2 virus vaccine is safe with no major reactions detected in the participants. This is a new strategy for vaccine development against COVID-19, and could be a backup plan if the approach targeting viral spike protein strategy that is being used in most other vaccine development fails. The study also suggested that this inactivated vaccine induces an immune response against several viral antigens. However, the efficacy of this vaccine needs to be tested in phases II and III trials.
Study design
randomized-controlled-trial
Study population and setting
This is a phase I randomized, double blinded, placebo-controlled trial of inactivated SARS-CO-V2 vaccine in adults aged between 18-59 years. The study included 191 healthy individuals divided into 8 groups, 24 participants each except for one group that had only 23 participants. Although the ethnicity of the participants was not mentioned, the study was conducted in China and presumably all the participants were Chinese. The participants were randomized into 2 broad groups: one group received the vaccination at days 0 and 14, while the other group received the vaccine at days 0 and 28. Each group was further divided into four subgroups that received either one of three different doses (50, 100, 150 EU) of the vaccine or a placebo. In addition to the safety of the vaccine, immunogenicity was also assessed by measuring the development of antibodies against different viral antigens and the expression and cytokine profiles in immune cells.
Summary of main findings
The study found the vaccine is generally safe with no severe adverse reactions detected in any of the participants for 28 days after the last vaccine inoculation. Mild reactions were seen in up to 33% of participants at the site of injection (pain, itching, redness and swelling) and systemic (fatigue, diarrhea, fever and rash). The vaccine did not cause an increase in the entry of the virus into immune cells, a phenomenon called antibody-dependent enhancement. Generally, the groups that received the vaccine at 0 and 14 days developed higher levels of neutralizing antibodies relative to the groups who received their vaccination at days 0 and 28. The expression profile of immune cells also showed upregulation of T cells, B cells and antigen presenting cells, suggesting their activation.
Study strengths
While most of the vaccines focus on SARS-CO-V2 spike protein that binds to ACE2 receptor, the vaccine tested in this study uses a different strategy. The study tested inactivated whole virion and showed that it induces antibodies against different viral antigens. Another strength is the concurrent testing of 2 different vaccination protocols (2 vaccine doses at 2 week and 4 week intervals) and three different doses. Finally, while the main purpose of phase I studies is to assess the safety, the study also investigated the immunogenicity of the vaccine.
Limitations
Most of the limitations are related to the nature of phase I trials, mainly due to the small number of participants. The study also did not include participants from COVID-19 high risk groups (older than 60 years or with diseases affecting the immune system). The assessment of cellular immune response was done indirectly by expression and cytokine profiles rather than directly testing the response of the immune cells to the viral antigens.
Value added
This study tested a new strategy for SARS-CO-V2 vaccine using the whole inactivated virion instead of viral spike protein that most other vaccines are targeting.
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SciScore for 10.1101/2020.09.27.20189548: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was reviewed and approved by the Ethics Committee of the West China Second University Hospital, Sichuan University.
Consent: Healthy volunteers 18 to 59 years of age were eligible for enrollment after providing informed consent.Randomization The enrolled participants were randomly assigned at a ratio of 1:1 to receive two inoculations at an interval of 14 days or 28 days, and the subjects in each schedule were assigned at a ratio of 1:1:1:1 to receive one of the three vaccine doses (50 EU, 100 EU and 150 EU) or the placebo. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not … SciScore for 10.1101/2020.09.27.20189548: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was reviewed and approved by the Ethics Committee of the West China Second University Hospital, Sichuan University.
Consent: Healthy volunteers 18 to 59 years of age were eligible for enrollment after providing informed consent.Randomization The enrolled participants were randomly assigned at a ratio of 1:1 to receive two inoculations at an interval of 14 days or 28 days, and the subjects in each schedule were assigned at a ratio of 1:1:1:1 to receive one of the three vaccine doses (50 EU, 100 EU and 150 EU) or the placebo. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The antibodies against SARS-CoV-2 are summarized as geometric mean titers with 95% CIs, and the cellular responses are presented as the proportion of positive responders. SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources The virus was proliferated in Vero cells (WHO) and was titrated with a microtitration assay. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources The statistical analysis was performed by an independent statistician using GraphPad Prism software (San Diego, CA, USA) and STATA software (Version 15.0; STATA Corp., College Station, TX, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)STATAsuggested: (Stata, RRID:SCR_012763)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:A limitation of this study is the lack of protective efficacy analysis and data from a parallel contrasting analysis of the transcriptome of PBMCs from individuals immunized with the vaccine and of those from COVID-19 patients, which was due to a lack of samples.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04412538 Recruiting Safety and Immunogenicity Study of an Inactivated SARS-CoV-2… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 25. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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