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. 2023 Oct 5;8(1):151.
doi: 10.1038/s41541-023-00745-4.

COVID-19 mRNA vaccine-mediated antibodies in human breast milk and their association with breast milk microbiota composition

Shilin Zhao #  1   2 , Kris Y W Lok #  3 , Zhen Y Sin  4   5 , Ye Peng  1   4 , Heidi S L Fan  6 , Nitya Nagesh  6 , Martha S L Choi  6 , Jojo Y Y Kwok  6 , Edmond P H Choi  6 , Xi Zhang  4   5 , Hogan Kok-Fung Wai  7   8 , Leo C H Tsang  7 , Samuel S M Cheng  7 , Matthew K L Wong  1 , Jie Zhu  1 , Chris K P Mok  4   5 , Siew C Ng  1   2   9 , Francis K L Chan  1   10 , Malik Peiris  7   8 , Leo L M Poon  7   8 , Hein M Tun  11   12   13
Affiliations

COVID-19 mRNA vaccine-mediated antibodies in human breast milk and their association with breast milk microbiota composition

Shilin Zhao et al. NPJ Vaccines. .

Abstract

Newborns can acquire immunological protection to SARS-CoV-2 through vaccine-conferred antibodies in human breast milk. However, there are some concerns around lactating mothers with regards to potential short- and long-term adverse events and vaccine-induced changes to their breast milk microbiome composition, which helps shape the early-life microbiome. Thus, we sought to explore if SARS-CoV-2 mRNA vaccine could change breast milk microbiota and how the changes impact the levels of antibodies in breast milk. We recruited 49 lactating mothers from Hong Kong who received two doses of BNT162b2 vaccine between June 2021 and August 2021. Breast milk samples were self-collected by participants pre-vaccination, one week post-first dose, one week post-second dose, and one month post-second dose. The levels of SARS-CoV-2 spike-specific IgA and IgG in breast milk peaked at one week post-second dose. Subsequently, the levels of both antibodies rapidly waned in breast milk, with IgA levels returning to baseline levels one month post-second dose. The richness and composition of human breast milk microbiota changed dynamically throughout the vaccination regimen, but the abundances of beneficial microbes such as Bifidobacterium species did not significantly change after vaccination. Additionally, we found that baseline breast milk bacterial composition can predict spike-specific IgA levels at one week post-second dose (Area Under Curve: 0.72, 95% confidence interval: 0.58-0.85). Taken together, our results identified specific breast milk microbiota markers associated with high levels of IgA in the breast milk following BNT162b2 vaccine. Furthermore, in lactating mothers, BNT162b2 vaccines did not significantly reduce probiotic species in breast milk.

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Conflict of interest statement

F.K.L.C. is Board Member of CUHK Medical Centre. He is a co-founder, non-executive Board Chairman, non-executive scientific advisor, Chief Medical Officer and shareholder of GenieBiome Ltd. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. S.C.N. has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. S.C.N. has received research grants through her affiliated institutions from Olympus, Ferring, and Abbvie. S.C.N. is a founder member, non-executive director, non-executive scientific advisor, and shareholder of GenieBiome Ltd. S.C.N. and H.M.T. receive patent royalties through her affiliated institutions. F.K.L.C., S.C.N., H.M.T. are named inventors of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. Other authors declare no financial or non-financial competing interests.

Figures

Fig. 1
Fig. 1. Study design and changes in immune responses to BNT162b2 vaccine, alpha diversity, and beta diversity in breast milk.
a Study design. b Immunoglobulin (Ig)A–dominant humoral response detected in the breast milk of women who received BNT162b2. c Immunoglobulin (Ig)G–dominant humoral response detected in the breast milk of women who received BNT162b2. Comparison of levels of receptor-binding domain (RBD)–specific IgA (B) and IgG (C) in breast milk before and after vaccination. p values were given by Paired Wilcoxon rank-sum tests (two-sides) and adjusted for FDR. d Beta diversity was significantly different before and after completion of the vaccination regimen. p values were given by PERMANOVA and adjusted for FDR. e Alpha diversity based on species diversity (Chao1) pre- and post-vaccination. p values were given by linear mixed modeling adjusting by maternal age and time interval between two doses of vaccination (two-sided). f Alpha diversity based on species diversity (Shannon) pre- and post-vaccination. p values were given by linear mixed modeling adjusting by maternal age and time interval between the two vaccine doses (two-sided). g Venn diagram showing the trajectory of differential species between pre-vaccination and post-vaccination. The differential species were identified by the LEfSe (LDA score >1.5 and p value < 0.05). Elements on boxplots: centre line, median; box limits, upper and lower quartiles; whiskers, 1.5×IQR.
Fig. 2
Fig. 2. Baseline breast milk microbiota composition in mothers with high and low responses at one week post-second dose of BNT162b2 (N = 43; High IgA: 18, Low IgA: 25).
a Bacteria diversity. b Bacteria richness. P values were given by Wilcoxon rank-sum test. c Principal coordinates analysis (PCoA) of breast milk microbiota composition of mothers with high- and low-IgA levels at one week post-second dose BNT162b2. p value was given by PERMANOVA. d Linear discriminant analysis effect size analysis of discriminant taxa in baseline breast milk microbiome of mothers with high and low-IgA levels at one week post-second dose of BNT162b2. LDA linear discriminant analysis. Elements on boxplots: centre line, median; box limits, upper and lower quartiles; whiskers, 1.5×IQR.
Fig. 3
Fig. 3. Breast milk microbiota composition in mothers with high and low responses at one week post-second dose of BNT162b2 (N = 43; High IgA: 18, Low IgA: 25).
a Bacteria diversity. b Bacteria richness. P value comparing the diversity and richness were given by Wilcoxon rank-sum test. c Principal coordinates analysis (PCoA) of breast milk microbiota composition of mothers with high- and low-IgA levels at one week post-second dose of BNT162b2. p value was given by PERMANOVA. d Linear discriminant analysis effect size analysis of discriminant taxa in breast milk microbiome of mothers with high- and low-IgA levels at one week post-second dose of BNT162b2. LDA linear discriminant analysis. Elements on boxplots: centre line, median; box limits, upper and lower quartiles; whiskers, 1.5×IQR.
Fig. 4
Fig. 4. Baseline breast milk bacterial species and functions associated with high- and low-IgA participants to BNT162b2 vaccination at one week post-second vaccine dose (N = 43; High IgA: 18, Low IgA: 25).
a AUROC (95% CI) values of models based on metagenomic markers, demographical markers (maternal age, different time interval between two doses of vaccine, and the use of epidural anesthesia), and combined markers using a random forest classification approach. AUROC, area under the receiver operating characteristic curve. The performance of random forest models was compared using the bootstrap method. b Baseline bacterial species and pathways associated with levels of immunoglobulin A. Differential baseline breast milk bacterial species and pathways were detected by a random forest model and Wilcoxon’s rank-sum test (two-sided), respectively. P values were given by Spearman’s correlation test.
Fig. 5
Fig. 5. Relative abundance of Bifidobacterium and Lactobacillus in breastmilk at different timepoints (Sample size, Baseline: 44, One week after 1st dose: 44, One week after 2nd dose: 43, One month after second dose: 44).
The median value was shown in different colors by different timepoints. p values were given by Paired Wilcoxon rank-sum tests (two-sides) and adjusted for FDR.
See this image and copyright information in PMC

References

    1. Khandia R, et al. Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ. Res. 2022;209:112816. doi: 10.1016/j.envres.2022.112816. - DOI - PMC - PubMed
    1. Nathanielsz, J., Toh, Z. Q., Do, L. A. H., Mulholland, K. & Licciardi, P. V. SARS-CoV-2 infection in children and implications for vaccination. Ped. Res.10.1038/s41390-022-02254-x (2022). - PMC - PubMed
    1. Medicine, A. O. B. Considerations for COVID-19 Vaccination in Lactation, https://www.bfmed.org/abm-statement-considerations-for-covid-19-vaccinat... Accessed Feburary 16, 2023 (2020).
    1. Gynecologists, T. A. C. O. O. A. COVID-19 Vaccination Considerations for Obstetric–Gynecologic Care. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articl... Accessed Feburary 16, 2023 (2023).
    1. Prevention, C. F. D. C. A. COVID-19 Vaccines While Pregnant or Breastfeeding, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregn... Accessed Feburary 16, 2023 (2022).