The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines

  1. Renee W. Y. Chan
  2. Shaojun Liu
  3. Jonathan Y. Cheung
  4. Joseph G. S. Tsun
  5. Kate C. Chan
  6. Kathy Y. Y. Chan
  7. Genevieve P. G. Fung
  8. Albert M. Li
  9. Hugh Simon Lam

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Abstract

Although the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity.

Objectives

This study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac).

Methods

Serial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac. The plasma and NELF immunoglobulins A and G (IgA and IgG) specific to SARS-CoV-2 S1 protein (S1) and their neutralization effects were quantified.

Results

Comirnaty induced nasal S1-specific immunoglobulin responses, which were evident as early as 14 ± 2 days after the first dose. In 64% of the subjects, the neutralizing effects of NELF persisted for at least 50 days. Moreover, 85% of Comirnaty recipients exhibited S1-specific IgA and IgG responses in plasma by 14 ± 2 days after the first dose. By 7 ± 2 days after the booster, all plasma samples possessed S1-specific IgA and IgG responses and were neutralizing. The induction of S1-specific plasma antibodies by CoronaVac was IgG dominant, and 83% of the subjects possessed S1-specific IgG by 7 ± 2 days after the booster, with neutralizing effects.

Conclusion

Comirnaty induces S1-specific IgA and IgG responses with neutralizing activity in the nasal mucosa; a similar response is not seen with CoronaVac.

Clinical Implication

The presence of a nasal response with mRNA vaccine may provide additional protection compared with inactivated virus vaccine. However, whether such widespread immunological response may produce inadvertent adverse effects in other tissues warrants further investigation.

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  1. Version published to 10.3389/fimmu.2021.744887
  2. ScreenIT

    SciScore for 10.1101/2021.06.15.21256661: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Consent was obtained from the participants and the study was approved by the Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee (CREC: 2021.214).
    IRB: Consent was obtained from the participants and the study was approved by the Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee (CREC: 2021.214).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The All statistical tests were performed using Graphpad version 9.1.2 for macOS.
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    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:
    The current study has the following limitations. First, the smaller sample size and the higher median age of the recipients of CoronaVac in the longitudinal group can be argued to have contributed towards the absence in NELF response and a slower and milder plasma response when compared to Comirnaty. We attempted to recruit the cross-sectional subjects to enrich our data for this important early report, while more subjects would be recruited for a better comparison. Second, we were using a SARS-CoV-2 surrogate virus neutralization test instead of a neutralization assay with live cells and viruses in Biosafety Level 3 settings. Therefore, the NAb measured in this study is a surrogate measure that is solely based on the inhibition of the binding between the SARS-CoV-2 antibody-mediated blockage of ACE2-spike (RBD) protein-protein interaction (30). The protective effects of the intracellular action of NELF IgA in the Comirnaty recipients or the plasma Ig specific to other SARS-CoV-2 proteins that theoretically should be manufactured in CoronaVac recipients were not considered. Although the surrogate assay used has been validated with the plaque reduction neutralization test (PRNT) utilizing the SARS-CoV-2 virus (31), the current test could underestimate the actual neutralization capacity. Third, we observed tremendous individual variations, for example, some recipients of Comirnaty were found to be IgA-, IgG- or IgA-IgG- for S1 protein. Although Comirnaty induced mucosal immunog...

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.06.15.21256661v1 on medRxiv