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

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 3

SARS-CoV-2–specific antibody and T cell responses change similarly in nonpregnant, pregnant, and lactating individuals.

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SARS-CoV-2–specific antibody and T cell responses change similarly in no...
(A) Dot plots showing anti-RBD IgG titers in Study B participants as determined by Luminex. Lines indicate paired samples from the same individuals. (B) Dot plots showing fold-changes of anti–SARS-CoV-2 RBD IgG antibody titers in postbooster as compared with prebooster samples among study participants. The individuals who were lactating for the duration of the study are indicated with open red circles. Data presented as mean ± SD. (C) Dot plots showing anti-RBD IgM and IgA titers in study participants as determined by Luminex. Lines indicate paired samples from the same individuals. NS, nonsignificant, as determined by 2-sided paired-sample t test. MFI, median fluorescence intensity. (D) Dot plots showing anti-RBD IgG and IgA titers in milk specimens from study participants as determined by ELISA. Lines indicate paired samples from the same individuals. (E and F) Dot plots showing percentages of SARS-CoV-2–specific CD4+ (E) or CD8+ (F) T cells among total CD4+ or CD8+ T cells in Study B participants. (G) SPICE analysis (see Supplemental Methods) showing frequencies of polyfunctional (colored) or monofunctional (shades of gray) SARS-CoV-2–specific CD4+ (top) and CD8+ (bottom) T cells from study participants. NS, nonsignificant as determined by permutation test. (H) t-SNE dot plots depicting SARS-CoV-2–specific CD4+ (top) and CD8+ (bottom) T cells from study participants. For all dot plots, P values were calculated by 2-sided paired-sample t tests, Wilcoxon’s matched-pairs signed-rank 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 = 8 pregnant, n = 7 pregnant, and n = 10 lactating participants.