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Pregnancy and lactation induce distinct immune responses to COVID-19 booster vaccination and SARS-CoV-2 breakthrough infection
Kailin Yin, … , Stephanie L. Gaw, Nadia R. Roan
Kailin Yin, … , Stephanie L. Gaw, Nadia R. Roan
Published July 22, 2025
Citation Information: JCI Insight. 2025;10(14):e191930. https://doi.org/10.1172/jci.insight.191930.
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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 1

Study design.

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Study design.
(A) Design for Study A comparing vaccine-elicited immune r...
(A) Design for Study A comparing vaccine-elicited immune responses in nonpregnant, pregnant, and lactating individuals. Blood specimens were procured from participants who had received 3 doses of an mRNA COVID-19 vaccine. The nonpregnant group (n = 10) consisted of biologically female participants of reproductive age (18–45 years old) not currently pregnant and/or lactating. The pregnant group (n = 10) consisted of individuals who were not pregnant at study initiation and pregnant at time of specimen collection. The lactating group (n = 18) consisted of 13 individuals who were pregnant at study initiation and lactating at the time of specimen collection, and 5 individuals who were lactating for the duration of the study. (B) Study B consisted of longitudinal sampling in a subset of the participants in panel A to compare changes in antigen-specific T cell responses in nonpregnant, pregnant, and lactating individuals following boosting. The nonpregnant group (n = 8) was comprised of participants not currently pregnant and/or lactating, and the pregnant group (n = 7) was comprised of individuals who were not pregnant at study initiation and pregnant during specimen collection. The lactating group (n = 10) was comprised of 8 individuals who were pregnant at study initiation and lactating during specimen collection, and 2 individuals who were lactating for the duration of the study. (C) Design for Study C comparing breakthrough versus vaccine-only immunity in pregnant and lactating individuals. Blood specimens were procured from pregnant (top) or lactating (bottom) participants who had received 3 doses of an mRNA COVID-19 vaccine with or without subsequent breakthrough infection with SARS-CoV-2. In the vaccinated-only group, pregnant individuals (n = 10) were comprised of individuals who were not pregnant at study initiation and pregnant at time of specimen collection. Lactating individuals (n = 18) were comprised of 13 individuals who were pregnant at study initiation and lactating at the time of specimen collection, and 5 individuals who were lactating for the duration of the study. In the breakthrough infection group, pregnant individuals (n = 10) were comprised of individuals who were not pregnant at study initiation and pregnant at time of specimen collection. Lactating individuals (n = 7) were comprised of 6 individuals who were pregnant at study initiation and lactating at the time of specimen collection, and 1 individual who was lactating for the duration of the study. All groups were defined based on the physiological state of the participant at the time of sample collection. Indicated are the timelines of primary vaccination, boosting, breakthrough infection, and blood collection. All numeric values correspond to the mean.

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