RESUMEN
As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming followed by boosting with 100-g or 50-g mRNA-1273, Ad26.COV2.S single-dose priming followed by Ad26.COV2.S booster and BNT162b2 two-dose priming followed by BNT162b2 boosting; and two heterologous primary-booster combinations: BNT162b2 followed by Ad26.COV2.S and Ad26.COV2.S followed by BNT162b2. Neutralizing antibody (Nab) titers to D614G on the day of boost (baseline) were detected in 85-100% of participants, with geometric mean titers (GMT) of 71-343 in participants who received an mRNA vaccine series versus GMTs of 35-41 in participants primed with Ad26.OV2.S. Baseline NAb titers to Omicron were detected in 50-90% of participants who received an mRNA vaccine series (GMT range 12.8-24.5) versus 20-25% among participants primed with Ad26.COV2.S. The booster dose increased the neutralizing GMT in most combinations to above 1000 for D614G and above 250 for Omicron by Day 29. Homologous prime-boost Ad26.COV2.S had the lowest NAb on Day 29 (D614G GMT 128 and Omicron GMT 45). Results were similar between age groups. Most homologous and heterologous boost combinations examined will increase humoral immunity to the Omicron variant.
RESUMEN
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 SummaryThe breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.