Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination

  1. Carlos Sariol
  2. Petraleigh Pantoja
  3. Crisanta Serrano-Collazo
  4. Tiffany Rosa-Arocho
  5. Albersy Armina-Rodríguez
  6. Lorna Cruz
  7. E. Stone
  8. Teresa Arana
  9. Consuelo Climent
  10. Gerardo Latoni
  11. Dianne Atehortua
  12. Christina Pabon-Carrero
  13. Amelia Pinto
  14. James Brien
  15. Ana Espino

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Abstract

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

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  1. Version published to 10.3390/v13101972
  2. Version published to 10.1101/2021.06.02.21257975v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.06.02.21257975: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cohorts: Detection of SARS-CoV-2 IgM antibodies: CovIgM-Assay is an indirect ELISA for the determination of human IgM antibody class, which was optimized via checkerboard titration.
    human IgM
    suggested: None
    Detection of SARS-CoV-2 IgG antibodies: The IgG antibodies were detected and quantified by using the CovIgG-Assay (20).
    IgG
    suggested: None
    It is an indirect ELISA for quantitative determination of human IgG antibody class, which was optimized by checkerboard titration.
    human IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using GraphPad Prism 7.0 software (GraphPad Software, San Diego, CA, USA).
    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:
    One limitation of our work is the limited number of subjects followed up after natural infection or after vaccination. However, due to the still limited data available on immune response to SARS-CoV-2 infection, previous reports have made great contribution with a similar number of subjects as on this study (16, 18, 19, 21). Our results contrast with a report describing a short persistence of the Nabs in plasma donors (22) but are in agreement with recent work indicating that neutralizing antibodies may persist longer (1, 5, 23). We were able to show a similar trend in our cohort with sustained neutralizing activity during the frame time of this study and highly relevant, despite of the significant decline in the IgG titers. In addition, we found some subjects with undetectable IgG (n=6) and IgG titers (n=11) while retain measurable percentage of neutralization, from 32 to 76 %, with the surrogate assay. This scenario has been described before suggesting that SARS-CoV-2 serologic assays may be less well suited for surveillance versus prediction of serum neutralization potency, which at the same time, facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 (24). Our results suggest that this approach should be also implemented in the context of vaccine efficacy evaluation at population level. From a technical point of view the discrepancies between samples without detectable antibodies but with neutralizing capabilities may be explaine...

    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.

  4. Version published to 10.1101/2021.06.02.21257975v1 on medRxiv