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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 breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 messenger RNA (mRNA) vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor sequence overlap was limited between blood and breastmilk. Overabundant breastmilk clones were observed in all individuals, were diverse, and contained complementarity-determining regions in three sequences with known epitope specificity, including to SARS-CoV-2 spike. SARS-CoV-2 spike-specific T cell receptors were more frequent in breastmilk compared to blood and expanded in breastmilk following a 3rdmRNA 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 passive infant protection.

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Respiratory syncytial virus (RSV) infection is a significant cause of morbidity and mortality among infants aged younger than 1 year, adults aged 65 years or older, and immunocompromised persons. Limited data exist on RSV infection in pregnancy and further research is needed. Strides are being made to develop vaccines, including vaccines for maternal immunization, as well as monoclonal antibodies for disease prevention.