Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination

  1. Aubree Mades
  2. Prithivi Chellamathu
  3. Noah Kojima
  4. Lauren Lopez
  5. Melanie A. MacMullan
  6. Nicholas Denny
  7. Aaron N. Angel
  8. Marilisa Santacruz
  9. Joseph G. Casian
  10. Matthew Brobeck
  11. Nina Nirema
  12. Jeffrey D. Klausner
  13. Frederick Turner
  14. Vladimir I. Slepnev
  15. Albina Ibrayeva

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Abstract

COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.

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  1. Version published to 10.1038/s41598-021-03931-3
  2. ScreenIT

    SciScore for 10.1101/2021.05.06.21256403: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Verbal informed consent was obtained from each subject prior to enrollment in the study and any sample collection.
    Field Sample Permit: Curative Real-Time rRT-PCR SARS-CoV-2 Collection and Assay: Oral fluid specimens were collected according to the Curative Instructions for Use as described in the FDA-EUA rRT-PCR SARS-CoV-2 Assay which includes expectoration of upper respiratory tract fluid (i.e., 3-5 coughs).
    Sex as a biological variableEnrollment was offered to subjects 18 years of age and older who had received the first dose of the COVID-19 Moderna vaccine within the previous 3-7 days, excluding subjects considered vulnerable, such as pregnant people, nursing home residents or other institutionalized persons, prisoners, and persons without decisional capacity.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To quantify SARS-CoV-2 IgG antibodies in oral mucosal fluid and nasal samples, an S1-specific monoclonal IgG antibody with no known cross-reactivity to the S2 domain of the spike protein was used as a reference antibody.
    SARS-CoV-2 IgG
    suggested: None
    The standard curve was used to calculate the sample IgG antibody concentration from absorbance values at 450/630 nm from the ELISA assay.
    sample IgG
    suggested: None
    The absorbance signal from each sample is directly proportional to the IgG antibody concentration present in the oral fluid (Fig. 1).
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Data Analysis: All data analysis was performed using GraphPad Prism (GraphPad Prism Version 9.0.2) software.
    GraphPad Prism
    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:
    This study had several limitations. Due to our enrollment of health care workers, the average age of participants was low, with only 8 participants over the age of 50 years and only 1 participant over the age of 65 years. Participants were not monitored during specimen collection after the first time point, but the ability of participants to follow instructions for unobserved collection was validated internally prior to sample collection. All participants received the Moderna COVID-19 vaccine, and further research is needed to understand the longitudinal antibody response in oral or nasal mucosal fluid following other COVID-19 vaccines, such as the mRNA Pfizer/BioNtech vaccine and the viral vector Janssen vaccine. It is not yet known how oral mucosal fluid antibody titers are directly comparable to serum titers for the protection of infection or disease. Self-collected oral mucosal fluid specimens for SARS-CoV-2 quantification could have potential applications in monitoring population antibody seroprevalence and long-term immune response to COVID-19 vaccines. Quantification of SARS-CoV-2 IgG antibodies in oral fluid mucosal specimens of non-vaccinated individuals with previous SARS-CoV-2 infection demonstrated antibody persistence through 3.5 months without a significant decline. This may suggest persistence of SARS-CoV-2 IgG antibodies in oral mucosal fluid post-vaccination.

    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 10.1101/2021.05.06.21256403 on medRxiv