Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination

Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection. One-Sentence Summary The breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.