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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 7

Breakthrough infection diminishes activated, tissue-homing CD8+ T cells in pregnant individuals.

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Breakthrough infection diminishes activated, tissue-homing CD8+ T cells ...
(A and B) Percentages of total CD8+ T cells coexpressing activation/checkpoint markers PD1, CTLA4, and/or TIGIT among total (A) or Tcm (B) CD8+ T cells of participants from Study C. (C) Percentages of total CD8+ T cells coexpressing activation markers CD38, Ox40, and ICOS among total CD8+ T cells. (D) The frequencies of activated (CD38+Ox40+) CD8+ T cells negatively associate with anti-RBD IgG titers following breakthrough infection in pregnant but not lactating individuals. (E) The frequencies of CD8+ Tscm positively associate with anti-RBD IgA titers after breakthrough infection in lactating but not pregnant individuals. (F and G) Percentages of total (F) or Tcm (G) CD8+ T cells coexpressing tissue-homing chemokine receptors CXCR4, CCR5, CCR6, and CD29 among total CD8+ T cells of study participants. For all panels, individuals who were lactating for the duration of the study are indicated with open circles colored brown (vaccination group) and purple (breakthrough infection group). For all dot plots, P values were calculated by 2-sided Student’s t test, Welch’s t test, or Mann-Whitney U test, depending on normality and equality of variance testing. For all correlation plots, r indicates Pearson’s correlation coefficient, and P values were determined by Pearson’s correlation tests. Data from this figure correspond to that generated from n = 10 vaccine and n = 10 breakthrough participants in the pregnant group, and n = 18 vaccine and n = 7 breakthrough participants in the lactating group.

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