BNT162b2 vaccination induces SARS-CoV-2 specific antibody secretion into human milk with minimal transfer of vaccine mRNA

  1. Jia Ming Low
  2. Yue Gu
  3. Melissa Shu Feng Ng
  4. Zubair Amin
  5. Le Ye Lee
  6. Yvonne Peng Mei Ng
  7. Bhuvaneshwari D/O Shunmuganathan
  8. Yuxi Niu
  9. Rashi Gupta
  10. Paul Anantharajah Tambyah
  11. Paul A MacAry
  12. Liang Wei Wang
  13. Youjia Zhong

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Importance

To examine the impact of SARS-CoV-2 vaccination of lactating mothers on human milk

Objective

(1) To quantify SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in human milk of lactating mothers who received the BNT162b2 vaccine, with reference to a cohort convalescent from antenatal COVID-19, and healthy lactating mothers. (2) To detect and quantify vaccine mRNA in human milk after BNT162b2 vaccination.

Design

Gestational Immunity For Transfer 2 (GIFT-2) is a prospective cohort study of lactating mothers who were due to receive two doses of BNT162b2 vaccine, recruited between 5th February 2021 and 9th February 2021.

Setting

Lactating healthcare workers living in Singapore

Participants

Convenience sample of ten lactating healthcare workers. Human milk samples were collected at four time points: pre-vaccination, 1-3 days after dose one, 7-10 days after dose one, and 3-7 days after dose two of the BNT162b2 vaccine.

Exposure

Two doses of the BNT162b2 vaccine 21 days apart.

Main Outcome and Measure

(i) SARS-CoV-2-specific IgA and IgG in human milk of lactating mothers who received BNT162b2 vaccine, (ii) Detection and quantification of vaccine mRNA in human milk after BNT162b2 vaccination.

Results

Ten lactating healthcare workers aged 32.5 years (range 29 – 42) were recruited, with 40 human milk samples collected and analysed. SARS-CoV-2-specific IgA was predominant in human milk of lactating mothers who received BNT162b2 vaccine. The sharpest rise in antibody production was 3 −7 days after dose two of the BNT162b2 vaccine, with medians of 1110 picomolar of anti-SARS-CoV-2 spike and 374 picomolar of anti-Receptor Binding Domain IgA. Vaccine mRNA was detected only on rare occasions, at a maximum concentration of 2 ng/mL.

Conclusions and Relevance

In this cohort of ten lactating mothers following BNT162b2 vaccination, nine (90%) produced SARS-CoV-2 IgA, and ten (100%) produced IgG in human milk with minimal amounts of vaccine mRNA. Lactating individuals should continue breastfeeding in an uninterrupted manner after receiving mRNA vaccination for SARS-CoV-2.

Trial Registration

Registered at clinicaltrials.gov ( NCT04802278 ).

Key Points

Question

Does BNT162b2 (i) induce the production and secretion of SARS-CoV-2 specific antibodies into human milk, and/or (ii) get secreted into human milk?

Findings

In this cohort that included ten lactating healthcare workers following BNT162b2 vaccination, 90% produced SARS-CoV-2 immunoglobulin A, and 100% produced immunoglobulin G in human milk, with minimal amounts of vaccine mRNA transfer.

Meaning

Lactating individuals should continue breastfeeding in an uninterrupted manner after receiving SARS-CoV-2 mRNA vaccination.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.04.27.21256151: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the Institutional Review Board (Gestational Immunity For Transfer GIFT-2: DSRB Reference Number: 2021/00095) and the study protocol was registered at clinicaltrials.gov (NCT04802278).
    Sex as a biological variableHuman milk samples at 1 month postpartum from convalescent and healthy mothers were also analysed for reference.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    A human monoclonal antibody specific for SARS-CoV-2 was recombinantly engineered and expressed as human IgG1 and/or IgA1.
    human IgG1
    suggested: None
    IgA1
    suggested: None
    Software and Algorithms
    SentencesResources
    Clinical characteristics of the cohorts were summarised using GraphPad Prism 8.
    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 has limitations. Firstly, we did not perform any functional assays; however, binding affinity of spike- and RBD-specific antibodies have been correlated with neutralization.2 Secondly, the relatively short duration of follow-up period also did not allow for characterization of durability of IgA in human milk after vaccination. Sample collection is ongoing for subsequent studies on antibody durability. These results lend immunological and clinical evidence to the current recommendation of the ACOG, RCOG and WHO that lactating individuals should continue breastfeeding in an uninterrupted manner after receiving COVID-19 mRNA vaccines.7,8,22

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04802278RecruitingGestational Immunity for Transfer

    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.

  2. Version published to 10.1101/2021.04.27.21256151v1 on medRxiv