Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA

  1. Miri Stolovich-Rain
  2. Sujata Kumari
  3. Ahuva Friedman
  4. Saveliy Kirillov
  5. Yakov Socol
  6. Maria Billan
  7. Ritesh Ranjan Pal
  8. Kathakali Das
  9. Peretz Golding
  10. Esther Oiknine-Djian
  11. Salim Sirhan
  12. Michal Bejerano Sagie
  13. Einav Cohen-Kfir
  14. Naama Gold
  15. Jamal Fahoum
  16. Manoj Kumar
  17. Maya Elgrably-Weiss
  18. Bing Zhou
  19. Miriam Ravins
  20. Yair E. Gatt
  21. Saurabh Bhattacharya
  22. Orly Zelig
  23. Reuven Wiener
  24. Dana G. Wolf
  25. Hila Elinav
  26. Jacob Strahilevitz
  27. Dan Padawer
  28. Leah Baraz
  29. Alexander Rouvinski

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Abstract

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

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  1. Version published to 10.3389/fimmu.2022.933347
  2. ScreenIT

    SciScore for 10.1101/2022.02.17.480851: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was part of an ongoing study and was reviewed by the Institutional Review Board (0278-18-HMO).
    Consent: All the participants provided written informed consent.
    Sex as a biological variableEligible participants were both male and female adults prior to or after receiving the BNT162b2 vaccine.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Sandwich ELISA for total IgG or IgA: MAXISORB 96 wells plates were coated ON with secondary anti-IgG or anti-IgA antibodies, blocked as for direct ELISA and incubated for 30 min with sera and saliva samples, serially diluted in blocking buffer.
    total IgG
    suggested: None
    anti-IgG
    suggested: None
    anti-IgA
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: Vero E6 and HEK293T cell lines were obtained from the American Type Culture Collection (
    Vero E6
    suggested: None
    HEK293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Vero E6 and 293T cells were grown in DMEM medium supplemented with 10% (v/v
    293T
    suggested: None
    P0 generation was produced according to the original Michael Whitt(Whitt, 2010) protocol with minor modification, using co-transfection of the 5 plasmids (pVSV-ΔG-GFP, pBS-N-Tϕ, pBS-P-Tϕ, pBS-L-Tϕ and pBS-G) into HEK293 cells.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Recombinant DNA
    SentencesResources
    Constructs and plasmids: The following plasmids were used for VSV-pseudovirus production: pVSV-ΔG-GFP, pCAGGS-G or pBS-N-Tϕ, pBS-P-Tϕ, pBS-L-Tϕ and pBS-G(Whitt, 2010).
    pVSV-ΔG-GFP
    suggested: None
    pCAGGS-G
    suggested: None
    pBS-L-Tϕ
    suggested: None
    pBS-G(Whitt
    suggested: None
    The plasmids for expression of the Receptor Binding Domain of SARS-CoV2 spike (RBD) and full-length spike (SARS-CoV-2 S (Δ19 aa) were cloned into the pcDNA3.4 backbone (Thermo).
    pcDNA3.4
    suggested: RRID:Addgene_131198)
    P0 generation was produced according to the original Michael Whitt(Whitt, 2010) protocol with minor modification, using co-transfection of the 5 plasmids (pVSV-ΔG-GFP, pBS-N-Tϕ, pBS-P-Tϕ, pBS-L-Tϕ and pBS-G) into HEK293 cells.
    pBS-N-Tϕ
    suggested: None
    pBS-P-Tϕ
    suggested: None
    pBS-G
    suggested: None
    P1 generation of VSV-G pseudotyped VSVdeltaG-GFP particles was generated by transfection of pCAGGS-VSV(G), followed by infection with P0 particles.
    pCAGGS-VSV(G
    suggested: None
    Software and Algorithms
    SentencesResources
    The images were captured from several fields of each well and the green cells were calculated by using automated image analysis by ImageJ (NIH).
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)
    The graphs were plotted to get the 50% neutralization titer (NT50), in GraphPad Prism.
    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: 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:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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 10.1101/2022.02.17.480851v1 on bioRxiv