Defining the contribution of breast milk immunoglobulins to infant immunity 2309834

Abstract

Abstract Introduction Infants inherit far more from their mothers than just half of their genes. They also receive mitochondrial DNA, the first seeds of their microbiome, and (perhaps) most remarkably maternal immunological memories as antibodies transferred via breast milk. Despite its importance, the immunological composition of breast milk its role in shaping the developing infant immune system remain poorly understood. Mothers carry a lifetime of distinct antibody specificities, each one recognizing a different pathogen such as virus, bacterium, toxin or vaccine antigen. Yet only a subset of these antibodies is transferred into breast milk. How these antibodies are selected, and whether they shape subsequent vaccine responses in offspring remain unknown. This work will compare breast-milk antibody repertoires to the full maternal repertoire to define the rules governing immune inheritance in early life. Methods We will use the 10x Genomics single-cell platform to profile systemic and mammary-gland plasma cells in murine dams. In parallel, antibodies from breast milk and maternal serum will undergo de novo mass-spectrometry—based sequencing to identify CDR3 signatures and enable clonal mapping between maternal plasma cell repertoires and milk-transferred antibodies. To test whether breast milk antibody transfer is passive or actively programs infant immunity, we will cross foster pups between naïve and vaccinated mothers and immunize them with the same antigen to determine how maternally derived milk IgG shapes the magnitude, quality, and trajectory of subsequent vaccine responses. Results I hypothesize that the selective transfer of maternal IgG into breast milk has the capacity to influence the magnitude and quality of immune responses of IgG vaccine elicited responses in offspring. Conclusion Although IgG is the dominant vaccine-elicited isotype, it remains understudied in maternal-infant immunology. This study will inform strategies to optimize maternal vaccination and enhance early life immunity. Funding Source n/a. Topic Categories Vaccines and Immunotherapy (VAC)