Broad Cross-Reactive IgA and IgG against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection

  1. Jiong Wang
  2. Bridget E. Young
  3. Dongmei Li
  4. Antti Seppo
  5. Qian Zhou
  6. Alexander Wiltse
  7. Anna Nowak-Wegrzyn
  8. Katherine Murphy
  9. Kaili Widrick
  10. Nicole Diaz
  11. Joseline Cruz-Vasquez
  12. Kirsi M. Järvinen
  13. Martin S. Zand

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Abstract

It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n = 30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n = 45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14–28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.

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  1. Version published to 10.3390/vaccines10060980
  2. ScreenIT

    SciScore for 10.1101/2022.03.13.22272281: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study cohorts: This study was approved by the Institutional Review Boards (IRB) at the NYU Grossman School of Medicine (IRB i20-00601) and University of Rochester Medical Center (IRB STUDY00004889).
    Consent: All participants provided informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After washing, goat anti-human PE-conjugated IgG and IgA secondary antibodies (Southern Biotech, Cal No:2040-09, 2050-09) were used as the detection reagent.
    anti-human PE-conjugated IgG
    suggested: None
    IgA
    suggested: (SouthernBiotech Cat# 2050-09, RRID:AB_2795707)
    Data analysis and statistical methods: Spearman’s correlations were used to calculate the correlation matrix of the IgA and IgG antibodies concentrations against SARS-CoV-2 (SARS2) full spike, S1, S2, and RBD in both milk and blood.
    SARS-CoV-2
    suggested: None
    SARS2
    suggested: None
    Spearman’s correlations of IgA and IgG antibody levels between milk and blood were also calculated.
    IgG
    suggested: None
    The longitudinal anti-S, S1, S2, RBD, and anti-N SARS-CoV-2 specific IgA and IgG antibody responses elicited by COVID-19 mRNA vaccination in milk and fingerstick blood samples were examined using the generalized linear mixed-effects models.
    anti-S
    suggested: None
    anti-N SARS-CoV-2 specific IgA and IgG
    suggested: None
    Similarly, the longitudinal milk and blood HCoV-reactive IgA and IgG antibody levels against spike proteins of SARS-CoV-2, SARS-CoV-1, OC43, HUK1, 229E, and NL63 were also estimated through generalized linear mixed-effects models.
    SARS-CoV-1, OC43
    suggested: None
    HUK1
    suggested: None
    Software and Algorithms
    SentencesResources
    The calculation of IgG antibody concentrations against each HCoV virus strain was performed using the Bio-Plex Manager™ 6.2 software (Bio-Rad Co.,
    Bio-Plex
    suggested: None
    Manager™
    suggested: (?Manager, RRID:SCR_016865)
    Statistical analysis software SAS V9.4 (SAS Institute Inc., Cary, NC) was used for fitting the generalized linear mixed-effects models and corresponding pairwise comparisons.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The limitation of low antibody concentration of the fingerstick samples would be a technical challenge to measure the neutralizing antibodies against the OC43, HKU1 in in vitro assays. However, our previous work (20) demonstrated that milk neutralizing anti-SARS-CoV-2 antibodies could be induced by COVID-19 mRNA vaccination and SARS-CoV-2 infection.

    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 10.1101/2022.03.13.22272281 on medRxiv