Safety and immunogenicity of inactivated SARS-CoV-2 vaccine in high-risk occupational population: a randomized, parallel, controlled clinical trial

  1. Yongliang Feng
  2. Jing Chen
  3. Tian Yao
  4. Yue Chang
  5. Xiaoqing Li
  6. Rongqin Xing
  7. Hong Li
  8. Ruixue Xie
  9. Xiaohong Zhang
  10. Zhiyun Wei
  11. Shengcai Mu
  12. Ling Liu
  13. Lizhong Feng
  14. Suping Wang

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population.

Methods

In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis.

Results

A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0–14, 0–21, and 0–28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95% CI: 88.4–108.4) in the 0–14 group, which was significantly lower compared with 134.4 (95% CI : 123.1–145.7) in the 0–21 group ( P  < 0.001 vs 0–14 group) and 145.5 (95% CI : 131.3–159.6) in the 0–28 group ( P  < 0.001 vs 0–14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild.

Conclusions

Both a two-dose of inactivated SARS-CoV-2 vaccine at 0–21 days and 0–28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0–14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706. Registered 1 January 2021, www.chictr.org.cn .

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  1. Version published to 10.1186/s40249-021-00924-2
  2. ScreenIT

    SciScore for 10.1101/2021.08.06.21261696: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consents were obtained from all participants before enrollment.
    IRB: The protocol was approved by the Ethics Committee of Shanxi Provincial Center for Disease Control and Prevention and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.
    Sex as a biological variableExclusion criteria were participants with history or family history of allergy, convulsion, epilepsy, encephalopathy or psychosis; any intolerance or allergy to any component of the vaccine; known or suspected diseases including severe respiratory disease, severe cardiovascular disease, severe liver or kidney disease, medically uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg), complications of diabetes mellitus, malignancy, various acute diseases or acute episodes of chronic disease; various infectious, suppurative and allergic skin diseases; congenital or acquired immunodeficiency, other vaccination history within 14 days before vaccination, a history of coagulation dysfunction, a history of non-specific immunoglobulin injection within 1 month prior to enrollment, acute illness with fever (body temperature > 37.0°C); and being pregnant or breastfeeding.
    RandomizationStudy design and participants: We conducted a randomized, controlled clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Beijing Biological Products Institute Co., Ltd. in Taiyuan City, Shanxi Province, China.
    Blindingnot detected.
    Power AnalysisStatistical analysis: The study sample size of 360 participants provided 84.4% power to detect a difference of 5% (85% vs. 80%) of responders in the 0-21 and 0-28 vaccination groups compared with the 0-14 group, respectively in airport ground staff and public security officers.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The vaccines used in this study were inactivated vaccine (Vero Cell) produced by Beijing Biological Products Institute Co., Ltd. Demographic information (age, gender, body mass index (BMI), marital status, and education level), influenza vaccination history, smoking, drinking, and chronic diseases were collected via questionnaire investigation.
    Beijing Biological
    suggested: None
    Data were recorded using EpiData, and analyses were performed using SAS version 9.3 (SAS Institute, Cary, NC, USA).
    SAS Institute
    suggested: (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:
    Our study had several limitations. First, we only reported immune response data for the high-risk occupational population aged 18 to 59 years. Further studies are required to assess the immunogenicity of inactivated SARS-CoV-2 vaccine in various populations, including general population, older people, children and adolescents. Second, data on long-term immunogenicity is not yet available, and the ongoing trial will provide more information. Third, cellular immunity and immune memory were not measured in the current study which need to be further studied. In summary, a two-dose of inactivated SARS-CoV-2 vaccine at 0-21 days and 0-28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0-14 days regimen in high-risk occupational population. And the neutralizing antibody titer in 0-21 group was numerically higher than that in 0-28 group.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.08.06.21261696v1 on medRxiv