Multipathogen Analysis of IgA and IgG Antigen Specificity for Selected Pathogens in Milk Produced by Women From Diverse Geographical Regions: The INSPIRE Study

Abstract

Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli, Shigella spp., Salmonella enterica serovar Typhi, Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus, S. pneumoniae, and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.

Dynamics of the Gut Microbiome in Shigella -Infected Children during the First Two Years of Life

“…We and others have identified placentally acquired maternal antibodies to Shigella antibodies at birth ( 16 , 17 , 41 ). Shigella -specific antibodies have been found in breast milk ( 61 ). Host (infant) innate immunity also likely influences infection outcome.…”

The need to study human milk as a biological system

“…DNA aptamer-based proteomics appears to be a potential platform, although it requires validation and optimization for milk ( 86 ). For milk immunoglobulins, a proteome microarray has been used to characterize complex immune responses (IgA and IgG) to multiple pathogens, demonstrating a potential mechanism underlying the protective effects of human milk ( 87 ).…”

Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease

“…While breast-feeding is known to reduce the risk of S. pneumoniae and H. influenzae diseases such as OM ( 41 , 42 ), the specific protective role of antigen-specific antibodies in breast milk has not been specifically investigated. A recent study using protein microarray to measure antibodies to multiple pathogens in breast milk of mothers from low- and high-income countries identified high variability in antigen-specific IgG and IgA repertoires for S. pneumoniae depending on geography/socioeconomic status ( 43 ). The use of breast milk to impart immunity to the surrounding environment is yet to be harnessed for prevention of S. pneumoniae and H. influenzae infections i.e.…”