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

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhao S, Lok KYW, Sin ZY, Peng Y, Fan HSL, Nagesh N, Choi MSL, Kwok JYY, Choi EPH, Zhang X, Wai HK, Tsang LCH, Cheng SSM, Wong MKL, Zhu J, Mok CKP, Ng SC, Chan FKL, Peiris M, Poon LLM, Tun HM
Journal
NPJ vaccines
Year
2023
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.

Experiment 1


Needs review

Curated date: 2023/10/17

Curator: Cabidog

Revision editor(s): Cabidog, Folakunmi

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Breast , Milk Mamma,Mammary part of chest,Mammary region,Breast,Mammary gland milk,Milk
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to vaccine , timepoint response to vaccine,timepoint
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mothers at pre-vaccination timepoint
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mothers at post vaccination timepoints
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breastfeeding mothers at post vaccination timepoints; one week post-first dose, one week post second-dose, one month post-second dose.
Group 0 sample size Number of subjects in the control (unexposed) group
44
Group 1 sample size Number of subjects in the case (exposed) group
44
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
1.5

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 1g

Description: The most differentially abundant taxa in mothers throughout all post-vaccination timepoints; at one week post-first dose, one week post-second dose and one month post-second dose.

Abundance in Group 1: increased abundance in Mothers at post vaccination timepoints

NCBI Quality ControlLinks
Acinetobacter ursingii
Roseomonas gilardii
unclassified Brevundimonas
unclassified Gordonia (in: high G+C Gram-positive bacteria)
unclassified Paracoccaceae

Revision editor(s): Folakunmi

Signature 2

Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 1g

Description: The most differentially abundant taxa in mothers throughout all post-vaccination timepoints; at one week post-first dose, one week post-second dose and one month post-second dose.

Abundance in Group 1: decreased abundance in Mothers at post vaccination timepoints

NCBI Quality ControlLinks
Helicobacter rodentium
unclassified Allobaculum
unclassified Muribaculaceae
unclassified Ralstonia
unclassified Turicibacter

Revision editor(s): Folakunmi

Experiment 2


Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
response to vaccine response to vaccine
Group 0 name Corresponds to the control (unexposed) group for case-control studies
mothers at pre-vaccination
Group 1 name Corresponds to the case (exposed) group for case-control studies
High IgA mothers at one week post-second dose
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
breastfeeding mothers with high IgA at one week after receiving the second dose of the SARS-CoV-2 mRNA vaccine (BNT162b2).
Group 1 sample size Number of subjects in the case (exposed) group
18
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.004
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 2d

Description: differential abundance in baseline microbiota of mothers with high IgA at one week post second-dose of BNT162b2.

Abundance in Group 1: increased abundance in High IgA mothers at one week post-second dose

NCBI Quality ControlLinks
Cutibacterium granulosum
Fusobacterium
Neisseria elongata
Prevotella histicola
Ruminococcus callidus
unclassified Aggregatibacter
unclassified Neisseria
unclassified Oscillospiraceae
unclassified Sutterella
unclassified Castellaniella
Bacillota sensu stricto incertae sedis
unclassified Monoglobus
Stutzerimonas balearica
unclassified Arachnia
unclassified Stomatobaculum
unclassified Actinobacillus
Actinomyces massiliensis
unclassified Terrisporobacter
unclassified Alishewanella
Endobacter medicaginis

Revision editor(s): Folakunmi

Experiment 3


Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
pre-vaccination (baseline)
Group 1 name Corresponds to the case (exposed) group for case-control studies
low IgA mothers at one week post-second dose
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
breastfeeding mothers with low IgA at one week after receiving the second dose of the SARS-CoV-2 mRNA vaccine (BNT162b2).
Group 1 sample size Number of subjects in the case (exposed) group
25

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Needs review

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: figure 2d

Description: differential abundance in baseline microbiota of mothers with low IgA at one week post second-dose of BNT162b2.

Abundance in Group 1: increased abundance in low IgA mothers at one week post-second dose

NCBI Quality ControlLinks
unclassified Brevundimonas
unclassified Acinetobacter
Corynebacterium kroppenstedtii

Revision editor(s): Folakunmi

Experiment 4


Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mothers at pre-vaccination timepoint
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mothers at one week post-first dose
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breastfeeding mothers at one week after receiving the first dose of BNT162b2 vaccine.
Group 1 sample size Number of subjects in the case (exposed) group
44
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
1.5

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: supplementary table 3

Description: differential abundance of mothers one week after first dose of BNT162b2 when compared to baseline.

Abundance in Group 1: increased abundance in Mothers at one week post-first dose

NCBI Quality ControlLinks
Acinetobacter radioresistens
Acinetobacter ursingii
Eubacterium ventriosum
Haemophilus haemolyticus
Haemophilus parahaemolyticus
Roseomonas gilardii
unclassified Actinobacillus
unclassified Brevundimonas
unclassified Microbacterium
unclassified Paracoccaceae
unclassified Sphingomonadaceae
Acinetobacter soli
Caldibacillus thermoamylovorans
Empedobacter brevis
un_Allorhizobium-Neorhizobium�Pararhizobium-Rhizobiumun_Allorhizobium-Neorhizobium�Pararhizobium-Rhizobium
unclassified Anoxybacillus
unclassified Bacillus (in: firmicutes)
unclassified Bergeyella
un_CHKCI001un_CHKCI001
unclassified Duganella
unclassified Empedobacter
unclassified Enhydrobacter
unclassified Flavobacterium
unclassified Janthinobacterium
unclassified Providencia
unclassified Pseudarthrobacter
unclassified Shewanella
unclassified Sphingomonas

Revision editor(s): Folakunmi

Experiment 5


Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mothers at pre-vaccination timepoint (baseline)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mothers at one week post-second dose
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breastfeeding mothers at one week post-second dose of BNT162b2 vaccine.

Lab analysis

Statistical Analysis

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: supplementary table 3

Description: differential abundance of mothers at one week post second dose of BNT162b2 when compared to baseline.

Abundance in Group 1: increased abundance in Mothers at one week post-second dose

NCBI Quality ControlLinks
Acinetobacter baumannii
Acinetobacter soli
Acinetobacter ursingii
Brevundimonas olei
Epilithonimonas hominis
Eubacterium ventriosum
Moraxella atlantae
Moraxella porci
Paenibacillus macerans
Peredibacter starrii
Prevotella melaninogenica
Roseomonas gilardii
unclassified Acinetobacter
unclassified Actinobacillus
unclassified Brevundimonas
unclassified Chitinophagaceae
unclassified Gemmobacter
unclassified Gordonia (in: high G+C Gram-positive bacteria)
unclassified Klebsiella
unclassified Leptotrichia
unclassified Megamonas
unclassified Nautella
unclassified Neptunomonas
unclassified Ochrobactrum
unclassified Paracoccaceae
unclassified Peptoniphilus
unclassified Pseudarthrobacter
unclassified Saccharofermentans
unclassified Serratia (in: enterobacteria)
unclassified Vogesella
uncultured Clostridia bacterium
uncultured Paraburkholderia sp.

Revision editor(s): Folakunmi, ChiomaBlessing

Experiment 6


Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mothers at pre-vaccination timepoint
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mothers at one month post second-dose
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breastfeeding mothers at one month post second-dose of BNT162b2 vaccine.

Lab analysis

Statistical Analysis

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, Chinelsy, ChiomaBlessing

Source: supplementary table 3

Description: differential abundance of mothers at one month post second dose of BNT162b2 when compared to baseline.

Abundance in Group 1: increased abundance in Mothers at one month post second-dose

NCBI Quality ControlLinks
Acinetobacter ursingii
Campylobacter showae
Dubosiella newyorkensis
Epilithonimonas hominis
Marinobacterium marisflavi
Moraxella atlantae
Neisseria elongata
Prevotella histicola
Prevotella melaninogenica
Pseudoroseomonas aestuarii
Roseomonas gilardii
Stenotrophomonas acidaminiphila
unclassified Acidovorax
unclassified Aeromicrobium
unclassified Atopobium
unclassified Brevundimonas
unclassified Corynebacteriaceae
unclassified Dermacoccaceae
unclassified Formosa
unclassified Gordonia (in: high G+C Gram-positive bacteria)
unclassified Lachnoanaerobaculum
unclassified Microvirga
unclassified Moraxella
unclassified Neisseriaceae
unclassified Novosphingobium
unclassified Paracoccaceae
unclassified Pasteurellaceae
unclassified Pediococcus
unclassified Planococcaceae
unclassified Pseudarcobacter
unclassified Rhizobiaceae
unclassified Serratia (in: enterobacteria)
unclassified Skermanella
unclassified Sphingomonas
unclassified Tepidimonas
uncultured Clostridia bacterium
un-Allorhizobium-Neorhizobium Pararhizobium-Rhizobiumun-Allorhizobium-Neorhizobium Pararhizobium-Rhizobium

Revision editor(s): Folakunmi, Chinelsy, ChiomaBlessing