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

## TL;DR

Pregnancy and lactation change the features of immune responses to COVID-19 vaccines and infections, possibly to protect the fetus or infant.

## Contribution

The study reveals distinct immune adaptations during pregnancy and lactation in response to vaccination and infection.

## Key findings

- Pregnancy increases stem-like CD4+ T cells after vaccination.
- Breakthrough infection during lactation boosts mucosal IgA, while during pregnancy it boosts IgG.
- Lactation reduces activated T cells, possibly due to cell trafficking to mammary glands.

## 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.

While pregnancy and lactation do not affect quantities of vaccine-elicited antibodies and T cells, they affect their features, with implications for mucosal and long-lived immunity.