Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination

  1. Suvichada Assawakosri
  2. Sitthichai Kanokudom
  3. Nungruthai Suntronwong
  4. Chompoonut Auphimai
  5. Pornjarim Nilyanimit
  6. Preeyaporn Vichaiwattana
  7. Thanunrat Thongmee
  8. Thaneeya Duangchinda
  9. Warangkana Chantima
  10. Pattarakul Pakchotanon
  11. Donchida Srimuan
  12. Thaksaporn Thatsanatorn
  13. Sirapa Klinfueng
  14. Ritthideach Yorsaeng
  15. Natthinee Sudhinaraset
  16. Nasamon Wanlapakorn
  17. Juthathip Mongkolsapaya
  18. Sittisak Honsawek
  19. Yong Poovorawan

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Abstract

Background

The use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants.

Methods

A total of 224 individuals who completed the 2-dose CoronaVac for 6 months were included. We studied reactogenicity and immunogenicity after a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the messenger ribonucleic acid (mRNA) vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-month boosting intervals.

Results

The solicited adverse events were mild to moderate and well tolerated. Total receptor binding domain (RBD) immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T-cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222, and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval group.

Conclusions

All 4 booster vaccines significantly increased binding and neutralizing antibodies in individuals immunized with 2 doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant.

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  1. Version published to 10.1093/infdis/jiac092
  2. ScreenIT

    SciScore for 10.1101/2022.01.28.22269986: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was approved by the Institutional Review Board of the Faculty of Medicine of Chulalongkorn University (IRB numbers 546/64) and was performed according to the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines (ICH-GCP).
    Consent: Informed consent was obtained prior to participant enrolment.
    Field Sample Permit: Sample collection, total RBD Ig, and anti-RBD IgG/nucleocapsid assay: Peripheral venous blood samples were collected to measure the immune response, including the total Ig against RBD, IgG against RBD, and IgG against nucleocapsid (N) as previously described [24].
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The mixtures were then transferred to a 96-well plate containing confluent Vero cell monolayers and incubated for 2 hours, then 1.5% semi-solid carboxymethyl cellulose was added to limit virus diffusion and cells were incubated further at 37°C, 5% CO2.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: All statistical analyses were conducted using GraphPad Prism v9.0 (
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software, San Diego, CA, USA), the Statistical package for the social sciences (SPSS) v.22
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical package for the social sciences
    suggested: None
    2 (SPSS Inc., Chicago, IL, USA), and R v4.1.2.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    This study had some limitations. First, the study did not examine the phenotype of CD4+ and CD 8+ T cells. Moreover, the total IFN-γ level and the surrogate virus neutralization test reached the upper limit of detection assay in some samples. Thus, we could not estimate the exact cellular immune response following the third booster vaccine. Further study using more advanced techniques included activation-induced marker assays may resolve this issue. Moreover, long-term studies are needed to determine the durability of the booster vaccination. In summary, we report a robust total RBD Ig response and acceptable safety profile after implementing heterologous third booster vaccines. However, neutralizing activities against omicron variants and the T-cell response were reduced in BBIBP-boosted individuals compared to AZD1222, BNT162b2, and mRNA 1273-boosted individuals.

    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 10.1101/2022.01.28.22269986v1 on medRxiv