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

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15
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


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/17

Curator: Cabidog

Revision editor(s): Cabidog, Folakunmi, ChiomaBlessing

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,breast,Mammary gland milk,Milk,milk
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to vaccine , Timepoint Response to vaccine,response to vaccine,Timepoint,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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
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


Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

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

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

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


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to vaccine Response to vaccine,response to vaccine
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low IgA mothers at Baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
High IgA mothers at Baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breastfeeding mothers with high IgA at baseline
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
18

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
2

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

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Figure 2d

Description: Taxonomic differences in baseline microbiota between high- and low-IgA subjects.

Abundance in Group 1: increased abundance in High IgA mothers at Baseline

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

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2024/02/15

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure 2d

Description: Taxonomic differences in baseline microbiota between high- and low-IgA subjects.

Abundance in Group 1: decreased abundance in High IgA mothers at Baseline

NCBI Quality ControlLinks
Corynebacterium kroppenstedtii
unclassified Acinetobacter
unclassified Brevundimonas

Revision editor(s): ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low IgA mothers at one week post-second dose
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).

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/22

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Figure 3d

Description: Taxonomic differences in microbiota one week post-second dose between high- and low-IgA subjects

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

NCBI Quality ControlLinks
Bifidobacterium bifidum
Candidatus Marinarcus aquaticus
Streptococcus parasuis
unclassified Acidaminococcus
unclassified Bifidobacterium
unclassified Corynebacterium
unclassified Dorea
unclassified Eubacterium
unclassified Gemmobacter
unclassified Holdemanella
unclassified Leucobacter
unclassified Neptunomonas
unclassified Rhodobacter
unclassified Subdoligranulum
unclassified Vibrio

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2024/02/15

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure 3d

Description: Taxonomic differences in microbiota one week post-second dose between high- and low-IgA subjects

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

NCBI Quality ControlLinks
Acinetobacter soli
unclassified Brevundimonas

Revision editor(s): ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

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-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 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

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

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

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 soli
Acinetobacter ursingii
Caldibacillus thermoamylovorans
Empedobacter brevis
Eubacterium ventriosum
Haemophilus haemolyticus
Haemophilus parahaemolyticus
Roseomonas gilardii
unclassified Actinobacillus
unclassified Anoxybacillus
unclassified Bacillus (in: firmicutes)
unclassified Bergeyella
unclassified Brevundimonas
unclassified Duganella
unclassified Empedobacter
unclassified Enhydrobacter
unclassified Flavobacterium
unclassified Janthinobacterium
unclassified Microbacterium
unclassified Paracoccaceae
unclassified Providencia
unclassified Pseudarthrobacter
unclassified Shewanella
unclassified Sphingomonadaceae
unclassified Sphingomonas
Clostridiales bacterium CHKCI001
unclassified Gordonia (in: high G+C Gram-positive bacteria)
unclassified Sphingobacterium
unclassified Allorhizobium-Neorhizobium Pararhizobium-Rhizobiumunclassified Allorhizobium-Neorhizobium Pararhizobium-Rhizobium

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2024/02/15

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplementary Table 3

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

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

NCBI Quality ControlLinks
Acinetobacter baumannii
Lactobacillus intestinalis
unclassified Allobaculum
unclassified Bacilli
unclassified Comamonadaceae
unclassified Fusicatenibacter
unclassified Parabacteroides
unclassified Ralstonia
unclassified Turicibacter
unclassified Muribaculaceae

Revision editor(s): ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

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.
Group 1 sample size Number of subjects in the case (exposed) group
43

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

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
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 Serratia (in: enterobacteria)
unclassified Vogesella
uncultured Clostridia bacterium
uncultured Paraburkholderia sp.
Clostridiales bacterium
unclassified Eubacterium (in: firmicutes)
unclassified Pseudarcobacter
unclassified Sandaracinobacter

Revision editor(s): Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-15

Curated date: 2024/02/15

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplementary Table 3

Description: Differential abundance of mothers one week after second dose of BNT162b2 when compared to baseline.

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

NCBI Quality ControlLinks
Anaerococcus nagyae
Anaerococcus octavius
Arthrobacter russicus
Bacteroides caecimuris
Phocaeicola plebeius
Phocaeicola vulgatus
Clostridiaceae bacterium
unclassified Oscillospiraceae
Cutibacterium granulosum
Helicobacter rodentium
Ligilactobacillus aviarius
Pseudoxanthomonas kaohsiungensis
Rothia sp. (in: high G+C Gram-positive bacteria)
unclassified Eubacterium
unclassified A0389unclassified A0389
unclassified Akkermansia
unclassified Alcaligenes
unclassified Allobaculum
unclassified Bacilli
unclassified Bacteroides
unclassified Castellaniella
unclassified Bacillota
unclassified Colidextribacter
unclassified Coriobacteriaceae
unclassified Desulfovibrionaceae
unclassified Dubosiella
unclassified Faecalibacterium
unclassified Haliangium
unclassified Halomonadaceae
unclassified Halomonas
unclassified Kurthia
unclassified Lachnospiraceae
unclassified Lactobacillus
unclassified Muribaculaceae
unclassified Parabacteroides
unclassified Parasutterella
unclassified Peptostreptococcaceae
unclassified Prevotellaceae
unclassified Quinella
unclassified Ralstonia
unclassified Romboutsia
unclassified SUP05_clusterunclassified SUP05_cluster
unclassified Sutterella
unclassified Treponema
unclassified Turicibacter
uncultured Odoribacter sp.

Revision editor(s): ChiomaBlessing

Experiment 6


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-16

Curated date: 2023/10/24

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

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.
Group 1 sample size Number of subjects in the case (exposed) group
44

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-16

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
Clostridiales bacterium
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
unclassified chloroplastunclassified chloroplast

Revision editor(s): Folakunmi, Chinelsy, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-16

Curated date: 2024/02/16

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Joan Chuks

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: decreased abundance in Mothers at one month post second-dose

NCBI Quality ControlLinks
Anaerococcus octavius
Aquabacterium citratiphilum
Arthrobacter russicus
Bacteroides caecimuris
Bacteroides fragilis
Clostridiaceae bacterium
Comamonas aquatica
Enterococcus cecorum
Helicobacter rodentium
Leptotrichia sp.
Ligilactobacillus aviarius
Phocaeicola coprocola
Pseudoxanthomonas kaohsiungensis
Rothia sp. (in: high G+C Gram-positive bacteria)
Ruminococcus flavefaciens
unclassified Aerococcus
unclassified Akkermansia
unclassified Alcaligenes
unclassified Alistipes
unclassified Allobaculum
unclassified Anaerococcus
unclassified Bacillota
unclassified Bacteria
unclassified Bacteroides
unclassified Bdellovibrio
unclassified Castellaniella
unclassified Coriobacteriaceae
unclassified Desulfovibrionaceae
unclassified Dialister
unclassified Dubosiella
unclassified Enterobacteriaceae
unclassified Enterococcus
unclassified Exiguobacterium
unclassified Faecalibacterium
unclassified Faecalitalea
unclassified Flaviflexus
unclassified Haliangium
unclassified Halomonadaceae
unclassified Halomonas
unclassified Holdemanella
unclassified Klebsiella
unclassified Lachnoclostridium
unclassified Lachnospiraceae
unclassified Lautropia
unclassified Microbacterium
unclassified Monoglobus
unclassified Oscillibacter
unclassified Oscillospiraceae
unclassified Parasutterella
unclassified Prevotellaceae
unclassified Quinella
unclassified Ralstonia
unclassified Romboutsia
unclassified Roseburia
unclassified Ruminococcus
unclassified Saccharofermentans
unclassified Treponema
unclassified Turicibacter
uncultured Odoribacter sp.
unclassified A0389unclassified A0389
unclassified NK4A214_groupunclassified NK4A214_group
unclassified SUP05_clusterunclassified SUP05_cluster
uncultured Muribaculaceae bacterium

Revision editor(s): ChiomaBlessing, Joan Chuks