Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

  1. Jéromine Klingler
  2. Gregory S. Lambert
  3. Vincenza Itri
  4. Sean Liu
  5. Juan C. Bandres
  6. Gospel Enyindah-Asonye
  7. Xiaomei Liu
  8. Viviana Simon
  9. Charles R. Gleason
  10. Giulio Kleiner
  11. Hsin-Ping Chiu
  12. Chuan-Tien Hung
  13. Shreyas Kowdle
  14. Fatima Amanat
  15. Benhur Lee
  16. Susan Zolla-Pazner
  17. Chitra Upadhyay
  18. Catarina E. Hioe

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Abstract

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

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  1. Version published to 10.3389/fimmu.2021.759688
  2. Version published to 10.1101/2021.05.11.21256972v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.11.21256972: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For the C1q assay, beads with spike-Ab or RBD-Ab complexes were incubated with C1q Component from Human Serum (Sigma, #C1740) for 1 hour at room temperature, followed by an anti-C1q-PE antibody (Santa Cruz, #sc-53544 PE).
    anti-C1q-PE
    suggested: None
    For the C3d assay, Complement Sera Human (33.3%, Sigma, #S1764) was added to the beads for 1 hour at 37°C, followed by a biotinylated monoclonal anti-C3d antibody (Quidel, #A702).
    anti-C3d
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    After washing and centrifugation (2,000 g, 10 minutes), the beads (∼3⨯108 beads, 10 µL/well) were incubated with THP-1 cells (0.25×105 cells, 200 µL/well) for 16 hours.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were performed as designated in the figure legends using GraphPad Prism 8 (GraphPad Software, San Diego, CA).
    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: 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.

  4. Version published to 10.1101/2021.05.11.21256972v1 on medRxiv