Safety and Immunogenicity of the Third Booster Dose with Inactivated, Viral Vector, and mRNA COVID-19 Vaccines in Fully Immunized Healthy Adults with Inactivated Vaccine

  1. Sitthichai Kanokudom
  2. Suvichada Assawakosri
  3. Nungruthai Suntronwong
  4. Chompoonut Auphimai
  5. Pornjarim Nilyanimit
  6. Preeyaporn Vichaiwattana
  7. Thanunrat Thongmee
  8. Ritthideach Yorsaeng
  9. Donchida Srimuan
  10. Thaksaporn Thatsanatorn
  11. Sirapa Klinfueng
  12. Natthinee Sudhinaraset
  13. Nasamon Wanlapakorn
  14. Sittisak Honsawek
  15. Yong Poovorawan

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Abstract

The coronavirus disease 2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2), in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7–alpha, B.1.351–beta, and B.1.617.2–delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of IFN-ɣ secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.

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  1. Version published to 10.3390/vaccines10010086
  2. ScreenIT

    SciScore for 10.1101/2021.12.03.21267281: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: After receiving the additional dose, all study participants were monitored for safety and immunogenicity The study protocol was approved by the Institutional Review Board (IRB), Faculty of Medicine, Chulalongkorn University (IRB number 546/64), and this trial has been registered with the Thai Clinical Trials Registry (TCTR 20210910002).
    Consent: Informed consent was obtained before participant enrollment.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A second incubation is carried out using an enzyme-conjugated antihuman IgA catalyzing a color reaction to detect the bound antibodies.
    antihuman IgA
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, the HB02 strain is obtained by passaging and purification in Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    The virion is produced in genetically modified HEK293 cells.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Experimental Models: Organisms/Strains
    SentencesResources
    ChAdOx1-S/nCoV-19 (referred to as AZD1222) is a non-replicating chimpanzee adenovirus Oxford 1 vector vaccine presenting the SARS-CoV-2 spike protein (AZD1222).
    ChAdOx1-S/nCoV-19
    suggested: None
    Software and Algorithms
    SentencesResources
    The IgG anti-RBD was tested using chemiluminescent microparticle immunoassay (CMIA) – SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, Il.) according to the manufacturer’s instructions.
    Abbott Laboratories
    suggested: None
    2.4.2 IgG anti N assay: For the SARS-CoV-2 anti-nucleocapsid (anti-N) IgG, the serum fraction was also tested using the CMIA (Abbott Diagnostics, Sligo, Ireland).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis: The graphical representation and statistical analyses were carried out using GraphPad Prism version 7.0 for Microsoft Windows.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 number of caveats need to be mentioned in this study. First, the relatively small sample size limits the statistical power of our results. Therefore, multi-center prospective longitudinal investigations with larger sample sizes should be further investigated to determine whether the data represent more reliability and rare adverse events may be observed, such as thrombosis in AZD1222 and myocarditis in BNT162b2. Second, the combination and prime/boost interval of enrolled participants varied in individual studies. Third, we did not determine live virus focus reduction neutralization tests (FRNTs) in these subjects. However, neutralizing activity against SARS-CoV-2 WT and their variant strains has been examined by an ELISA-based surrogate virus neutralization test. Additionally, there were limitations in quantification of serum IgA as some of the values exceed the upper limit of quantification. Lastly, we did not evaluate the mucosal IgA that reflected the first line barrier against SARS-CoV-2 internalization. Further studies will be needed to overcome these limitations

    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 10.1101/2021.12.03.21267281v1 on medRxiv