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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 6

Breakthrough infection diminishes cytolytic SARS-CoV-2–specific CD8+ T cell frequencies and coordinates distinct adaptive immune responses in lactating individuals.

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Breakthrough infection diminishes cytolytic SARS-CoV-2–specific CD8+ T c...
(A) Percentages of CD107a+Perforin+ cells, CD107a+GzmB+ cells, and GzmB+Perforin+ cells among SARS-CoV-2–specific CD8+ T cells in pregnant (left) and lactating (right) participants of Study C. P values were calculated by Mann-Whitney U test or Welch’s t test, depending on normality and equality of variance testing. (B) The frequencies of cytolytic (CD107a+GzmB+) SARS-CoV-2–specific CD8+ T cells positively associate with anti-RBD IgA titers following breakthrough infection in pregnant but not lactating individuals. (C) The frequencies of SARS-CoV-2–specific CD4+ Tem cells positively associate with anti-N IgG titers following breakthrough infection in lactating but not pregnant individuals. (D) The frequencies of SARS-CoV-2–specific CD4+ Treg cells negatively associate with anti-N IgG titers following breakthrough infection in lactating but not pregnant individuals. 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 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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