Survival of Vaccine-Induced Human Milk SARS-CoV-2 IgG, IgA and SIgA Immunoglobulins across Simulated Human Infant Gastrointestinal Digestion

  1. Myrtani Pieri
  2. Maria-Arsenia Maniori
  3. Lucy Shahabian
  4. Elie Kanaan
  5. Irene Paphiti-Demetriou
  6. Spyros Pipis
  7. Kyriakos Felekkis
  8. Vicky Nicolaidou
  9. Christos Papaneophytou

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Abstract

Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, either after natural infection or vaccination, but whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers remains inconclusive. Herein, we evaluated the levels of IgG, IgA, and secretory IgA (SIgA) antibodies against the spike protein of SARS-CoV-2 in 43 lactating mothers who received at least two doses of either an mRNA-based vaccine (Pfizer/BioNTech, Moderna; n = 34) or an adenovirus-based vaccine (AstraZeneca; n = 9). We also accessed the potential persistence of SARS-CoV-2 IgA, IgG, and secretory IgA (SIgA) antibodies from vaccinated women in the GI tract of the infants by means of a static in vitro digestion protocol. Our data depict that, although slightly reduced, the IgA antibodies produced after vaccination resist both the gastric and intestinal phases of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. Additionally, SIgA antibodies were found to greatly resist the gastric phase of digestion albeit showing some reduction during the intestinal phase. The evaluation of the vaccine induced Ig profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract provide important information about the potential protective role of this form of passive immunity that could help decision making during the COVID-19 pandemic and beyond.

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  1. Version published to 10.3390/nu14163368
  2. ScreenIT

    SciScore for 10.1101/2021.06.17.21259021: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participants gave informed consent, and all procedures were approved by the Cyprus National Bioethics Committee (EEBK/EΠ /2021/24).
    IRB: Participants gave informed consent, and all procedures were approved by the Cyprus National Bioethics Committee (EEBK/EΠ /2021/24).
    Sex as a biological variable2.1 Study participants: Two lactating women were recruited in the present study that had no diagnosis of laboratory-confirmed COVID-19 in the past and were scheduled to receive a COVID-19 vaccine.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was performed using GraphPad Prism (v.8.0,
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software Inc.
    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: We detected the following sentences addressing limitations in the study:
    A limitation of this study is the fact that it describes a case report of solely two individuals so all results should be interpreted with caution, especially having in mind the great heterogeneity in the immune responses in different individuals (Weaver et al., 1998). We are in the process of obtaining more samples from lactating mothers as the vaccination program in Cyprus progresses. Also, this study did not measure IgA and IgG concentrations in the serum of the lactating mothers, something that could provide interesting information on the comparison of the antibody titers between serum and milk. The use of a single human milk sample to examine the survival of IgGs and IgAs in the simulated GI system also represents a limitation. Furthermore, the current protocol could not discriminate between IgAs and secretory IgAs in the milk samples, something that could be done in the future by employing specific antibodies to the secretory part of the SIgA. Further studies are needed to elucidate the correlation between IgA/SIgA and IgG levels after vaccination with the age of infant and duration of lactation as well as the nature of vaccine-elicited Igs based on the type of the vaccine. It has been proposed that the immunological profile of mother’s milk is dynamic and can be influenced by several factors including the week of gestation and lactation period (Czosnykowska-Łukacka et al., 2020b). Therefore, the age of the infant and the duration of lactation should also be taken into ...

    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

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  3. Version published to 10.1101/2021.06.17.21259021v1 on medRxiv