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Pregnancy and lactation induce distinct immune responses to COVID-19 booster vaccination and SARS-CoV-2 breakthrough infection
Kailin Yin, Lin Li, Xiaoyu Luo, Jason Neidleman, Arianna G. Cassidy, Yarden Golan, Nida Ozarslan, Christine Y. Lin, Unurzul Jigmeddagva, Mikias Ilala, Megan A. Chidboy, Mary Prahl, Stephanie L. Gaw, Nadia R. Roan
Kailin Yin, Lin Li, Xiaoyu Luo, Jason Neidleman, Arianna G. Cassidy, Yarden Golan, Nida Ozarslan, Christine Y. Lin, Unurzul Jigmeddagva, Mikias Ilala, Megan A. Chidboy, Mary Prahl, Stephanie L. Gaw, Nadia R. Roan
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Research Article Immunology Reproductive biology

Pregnancy and lactation induce distinct immune responses to COVID-19 booster vaccination and SARS-CoV-2 breakthrough infection

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Abstract

The widespread uptake of COVID-19 vaccines by women provided a unique opportunity to study the effects of pregnancy and lactation on immune responses to vaccination. Leveraging a cohort with well-defined SARS-CoV-2 exposure history, we found that the magnitude of humoral and cellular immune responses to vaccine-delivered SARS-CoV-2 spike was not affected by pregnancy or lactation status. However, vaccination during pregnancy elicited more stem-like SARS-CoV-2–specific CD4+ T cells. Moreover, breakthrough infection promoted spike-specific IgG in pregnant individuals in contrast with IgA in those lactating, suggesting that the pregnancy-to-lactation transition favors mucosal antibody responses. Breakthrough infection also reduced peripheral cytolytic SARS-CoV-2–specific CD8+ T cell frequencies during lactation but not pregnancy, which may reflect trafficking of the cells to mammary glands. Our study also uncovered an impact of pregnancy and lactation on global T cell phenotypes. In particular, lactating individuals preferentially exhibited a state of diminished T cell activation. Furthermore, breakthrough infection during pregnancy, but not lactation, diminished frequencies of activated CD8+ T cells, tissue-homing CD8+ T cells, and γδ T cells. Our findings support the notion that immunity during pregnancy and lactation adapts to benefit the fetus or breastfed infant, with implications for eliciting effective long-term immunity for these uniquely vulnerable groups.

Authors

Kailin Yin, Lin Li, Xiaoyu Luo, Jason Neidleman, Arianna G. Cassidy, Yarden Golan, Nida Ozarslan, Christine Y. Lin, Unurzul Jigmeddagva, Mikias Ilala, Megan A. Chidboy, Mary Prahl, Stephanie L. Gaw, Nadia R. Roan

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Figure 4

Pregnant individuals exhibit higher proportions of stem-like SARS-CoV-2–specific CD4+ T cells, while lactating individuals exhibit overall lower T cell activation.

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Pregnant individuals exhibit higher proportions of stem-like SARS-CoV-2–...
(A) Percentages of stem-like CD127+CCR7+ cells among SARS-CoV-2–specific (left) or total (right) CD4+ T cells from participants of Study A. (B) Mean signal intensity (MSI) of expression levels of activation markers CD38 and HLA-DR among total CD4+ (top) and CD8+ (bottom) T cells from study participants. (C) Percentages of activated (CD38+HLA-DR+) cells among total CD4+ or CD8+ T cells from study participants. In all plots, data are presented as mean ± SD, and dots represent individuals. Open red circles represent the individuals who were lactating for the duration of the study. P values were calculated by 1-way ANOVA corrected by Tukey’s multiple-comparison test, or Kruskal-Wallis H test corrected by Dunn’s multiple-comparison test, depending on normality and equality of variance testing. Data from this figure correspond to that generated from n = 10 nonpregnant, n = 10 pregnant, and n = 18 lactating participants.

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