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Publications

Journal Article Epublish

PubMed: 40693463 DOI: 10.1172/jci.insight.191930

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

JCI Insight 10(14)

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

Affiliations

  • Gladstone Institutes, San Francisco, California, USA. Department of Urology.
  • Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences. Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences.
  • Gladstone Institutes, San Francisco, California, USA.
  • Department of Urology.
  • Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences.
  • Department of Bioengineering and Therapeutic Sciences.
  • Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences.
  • Division of Experimental Medicine, Department of Medicine, and.
  • Division of Pediatric Infectious Diseases and Global Health, Department of Pediatrics, UCSF, San Francisco, California, USA.

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.

MeSH

Cells, Pregnancy, Lactation, Sars-Cov-2, Vaccines, Biomedical Research, Vaccination, Covid-19, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections, Breakthrough Infections