SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans

  1. David Forgacs
  2. Hyesun Jang
  3. Rodrigo B. Abreu
  4. Hannah B. Hanley
  5. Jasper L. Gattiker
  6. Alexandria M. Jefferson
  7. Ted M. Ross

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Abstract

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants ( p <0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants ( p =0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.

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  1. Version published to 10.3389/fimmu.2021.728021
  2. ScreenIT

    SciScore for 10.1101/2021.05.29.445137: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics statement and the role of the funding source: The study procedures, informed consent, and data collection documents were reviewed and approved by the WIRB-Copernicus Group Institutional Review Board (WCG IRB #202029060) and the University of Georgia.
    IRB: Ethics statement and the role of the funding source: The study procedures, informed consent, and data collection documents were reviewed and approved by the WIRB-Copernicus Group Institutional Review Board (WCG IRB #202029060) and the University of Georgia.
    Sex as a biological variableExclusion criteria included being younger than 18 years old, weighing less than 110 lbs, being pregnant, being cognitively impaired, or having anemia or a blood-borne infectious condition such as hepatitis C or HIV.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    At the pre-vaccination timepoint, 20 of them were categorized as immunologically naïve to SARS-CoV-2, and reported no specific COVID-19 symptoms, never had a positive NAAT result, and tested negative for RBD-specific IgG antibodies with concentrations below our experimentally determined threshold of 1.139μg/mL [see under ROC analysis heading] (Table S1A).
    SARS-CoV-2
    suggested: None
    RBD-specific IgG
    suggested: None
    Plates were washed 5 times with PBS/0.05% Tween20 and IgG antibodies were detected using horseradish peroxidase (HRP)-conjugated goat anti-human IgG detection antibody (Southern Biotech, Birmingham, AL, USA) at a 1:4,000 dilution and incubated for 90 min at 37°C.
    IgG
    suggested: None
    anti-human IgG
    suggested: None
    Linear regression and correlation analyses were applied to test the relationship between anti-RBD IgG antibody concentrations (ELISA) and VN endpoint titers.
    anti-RBD IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The serum-virus mixture was then transferred to Vero E6 cells in 96-well cell culture plates.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    All analyses were performed using GraphPad Prism 9.1.1.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analyses were performed using GraphPad 9.1.0, and statistical significance was represented by * p<0.05, ** p<0.01, *** p<0.001, and **** p<0.0001.
    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.
    • 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 10.1101/2021.05.29.445137v1 on bioRxiv