Human Milk, Bovine Milk and Bovine Milk-Based Formulae Show Diverse and Distinct Antigen Recognition Patterns

Background/Objectives: Human milk supports neonatal protection and immune maturation through a diverse repertoire of immunoglobulins. Antigen recognition profiling has shown geographic and interindividual variation in human milk IgA and IgG responses to global pathogens. In bovine milk, studies indicate that bovine immunoglobulins can recognize and inhibit human pathogens, but comprehensive antigen recognition profiles are lacking. Furthermore, bovine immunoglobulins are susceptible to heat-induced denaturation during milk processing and infant formula production. Therefore, this study compared antigen recognition patterns of human milk and bovine milk, and explored patterns of immunoglobulin-rich bovine milk ingredients (milk fat globule membrane-enriched whey and native whey protein concentrate) and bovine milk-based infant formulae. Methods: Antigen recognition patterns were determined using multipathogen protein microarrays containing 644 full-length or fragmented proteins representing a diverse set of pathogens relevant to human health. Results: Human milk IgA and IgG recognized the highest levels and breadth of pathogen antigens, while infant formulae recognized the least, although all bovine samples had antibodies against a subset of pathogens associated with common pediatric infections. Bovine milk-based ingredients were more similar in antigen recognition profiles to raw bovine milk, as was an infant formula that was gently processed. Conclusions: Human milk provides the highest levels and diversity of specific IgA and IgG antibodies to numerous pathogen antigens, unmatched by infant formulae, which highlights the unique capacity of breastfeeding in providing protection against a wide array of infections in infancy. The use of bovine milk ingredients rich in immunoglobulins and gentle processing may result in formulae that are closer in antibody composition to raw bovine milk than regular infant formulae. The clinical and public health relevance of the pool of antibodies in these bovine milk products in protecting infants from pediatric infections remains to be studied.