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
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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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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
Ethics not detected. Sex as a biological variable 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. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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. ACE2suggested: NoneThe reciprocal of the dilution that resulted in a binding inhibition rate of 20% or more (PI20) was defined as the neutralizing antibody … 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
Ethics not detected. Sex as a biological variable 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. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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. ACE2suggested: NoneThe reciprocal of the dilution that resulted in a binding inhibition rate of 20% or more (PI20) was defined as the neutralizing antibody titer. PI20suggested: NoneThe ELISPOT plates were coated with purified anti-mouse IFN-γ capture antibody and incubated overnight at 4 °C. anti-mouse IFN-γsuggested: NoneExperimental Models: Cell Lines Sentences Resources 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. Verosuggested: RRID:CVCL_A5BG)Experimental Models: Organisms/Strains Sentences Resources 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/csuggested: NoneRecombinant DNA Sentences Resources 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. pGX27suggested: NoneGX-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/ICsuggested: NonepGX27-SRBD-F/NPsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis: Data analyses were performed using GraphPad Prism 7 (GraphPad Software). GraphPadsuggested: (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.
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