Potentiating the cross-reactive IFN-γ T cell and polyfunctional T cell responses by heterologous GX-19N DNA booster in mice primed with either a COVID-19 mRNA vaccine or inactivated vaccine

  1. Yong Bok Seo
  2. Ara Ko
  3. Duckhyang Shin
  4. Junyoung Kim
  5. You Suk Suh
  6. Juyoung Na
  7. Ji In Ryu
  8. Young Chul Sung

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Abstract

Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potentials of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T-cells to the SARS-CoV-2 variant of concern (VOC) compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T-cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, heterologous GX-19N boost induced higher S-specific polyfunctional CD4 + and CD8 + T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.29.493923: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableMouse immunizations: Female BALB/c mice aged 6–8 weeks (Central Lab Animal) were intramuscularly immunized with 0.4 μg/animal VP vaccine (total volume of 50 μL, adjusted with PBS) at week 0.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Surrogate virus-neutralization assay: The sVNT was used to analyze the binding ability of RBD to ACE2 after neutralizing RBD with antibodies in the serum.
    ACE2
    suggested: None
    The reciprocal of the dilution that resulted in a binding inhibition rate of 20% or more (PI20) was defined as the neutralizing antibody titer.
    PI20
    suggested: None
    The ELISPOT plates were coated with purified anti-mouse IFN-γ capture antibody and incubated overnight at 4 °C.
    anti-mouse IFN-γ
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The inactivated SARS-CoV-2 vaccine produced from Vero cells contained 4 μg of viral antigens and 0.225 mg of aluminum hydroxide adjuvant in a 0.5-mL dose.
    Vero
    suggested: RRID:CVCL_A5BG)
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse immunizations: Female BALB/c mice aged 6–8 weeks (Central Lab Animal) were intramuscularly immunized with 0.4 μg/animal VP vaccine (total volume of 50 μL, adjusted with PBS) at week 0.
    BALB/c
    suggested: None
    Recombinant DNA
    SentencesResources
    Vaccines: The COVID-19 GX-19N DNA vaccine, consisting of GX-19 and GX-21 at a ratio of 1:2, was constructed by inserting the antigen genes of SARS-CoV-2 into a pGX27 vector.
    pGX27
    suggested: None
    GX-19 (pGX27-SΔTM/IC) contains the SARS-CoV-2 spike (S) gene lacking the transmembrane (TM)/intracellular (IC) domain, and GX-21 (pGX27-SRBD-F/NP) is designed to express the fusion protein of the receptor-binding domain (RBD) of the spike protein, the T4 fibritin C-terminal foldon (SRBD-Foldon), and the nucleocapsid protein (N).
    pGX27-SΔTM/IC
    suggested: None
    pGX27-SRBD-F/NP
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Data analyses were performed using GraphPad Prism 7 (GraphPad Software).
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study 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.
    • No funding statement was detected.
    • 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.

  2. Version published to 10.1101/2022.05.29.493923v1 on bioRxiv