Effects of boosted mRNA and adenoviral‐vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

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

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Abstract

The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination, because it harbors mutations. Here we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T‐cell responses. A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4–5 months were enrolled, to receive AZD1222, BNT162b2, or mRNA‐1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of severe acute respiratory syndrome coronavirus 2‐binding antibodies were measured using enzyme‐linked immunosorbent assay. The NAb titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon‐γ responses were measured to observe the T‐cell activation. A substantial loss in neutralizing potency to omicron variant was found at 4–5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA‐1273 followed by BNT162b2 and AZD1222. In addition, individuals boosted with messenger RNA (mRNA) vaccines develop a T‐cell response to spike protein, whereas those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events. Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T‐cell response.

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  1. Version published to 10.1002/jmv.28044
  2. ScreenIT

    SciScore for 10.1101/2022.04.25.22274294: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was reviewed and approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (IRB numbers 871/64) and performed under the Declaration of Helsinki and Good Clinical Practice principles.
    Consent: All participants signed a written consent before being enrolled in this study.
    Sex as a biological variablenot detected.
    RandomizationIn addition, a subset of samples was randomly selected to perform surrogate virus neutralization assay (sVNT
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement binding antibody and neutralizing activity using ELISA-based assay: All sera samples measured anti-RBD IgG and anti-nucleocapsid (N) IgG using enzyme-linked immunosorbent assays (Abbott Diagnostics, Abbott Park, IL).
    anti-nucleocapsid ( N
    suggested: None
    The anti-RBD IgG was expressed as a binding antibody unit (BAU/mL), and a value ≥ 7.1 was considered positive.
    anti-RBD IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The virus–sera mixtures were transferred to monolayers of Vero cells in a 96-well plate and incubated for 2 h.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Measurement binding antibody and neutralizing activity using ELISA-based assay: All sera samples measured anti-RBD IgG and anti-nucleocapsid (N) IgG using enzyme-linked immunosorbent assays (Abbott Diagnostics, Abbott Park, IL).
    Abbott
    suggested: None
    All statistical analyses were performed using SPSS v23.0
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Figures were generated using GraphPad Prism v9.0 (GraphPad, San Diego, CA) and R version 3.6.0 (R Foundation, Vienna, Austria).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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:
    Study limitations include the detection limits of the surrogate virus neutralization assay. Most boosted individuals elicited an elevation in antibody level that was higher than the upper limit of detection; thus, this method may not have provided the actual neutralizing antibody level in case of a robust immune response. Furthermore, the effect of omicron peptide stimulation on T-cell response was not examined. However, van Kessel et al. showed that no difference in cytokine production was observed upon stimulation with S-peptide pools derived from the ancestral strain and omicron variants [17]. Further studies are required to define long-term immunity and durability of immune responses against SARS-CoV-2 variants, particularly omicron subvariants, after administration of booster vaccinations. In conclusion, these findings indicate that booster vaccination could retain the level of anti-RBD IgG and improved the neutralizing activity against delta and omicron variants. Of note, a booster dose could induce neutralizing antibody titers to omicron BA.1 comparable to BA.2. Furthermore, individuals boosted with mRNA vaccines could induce IFN-γ responses higher than those boosted with AZD1222. Hence, giving mRNA vaccines as the booster dose could improve humoral and T-cell responses and induce neutralization coverage against omicron subvariants.

    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

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  3. Version published to 10.1101/2022.04.25.22274294v1 on medRxiv