Pregnancy reduces COVID-19 vaccine immunity against novel variants.

Pregnant women are at heightened risk for severe outcomes from infectious diseases like COVID-19, yet were not included in initial vaccine trials, which may contribute to low booster uptake (15% or lower). We explored the serological and cellular responses to COVID-19 mRNA booster vaccines (i.e., ancestral and BA.5) in pregnant and age-matched, non-pregnant females to identify how pregnancy affects immunity against the vaccine and novel variants. Antibodies from pregnant women were less cross-reactive to non-vaccine antigens, including XBB.1.5 and JN.1. Non-pregnant females showed greater IgG1:IgG3 ratios and neutralization against all variants. In contrast, pregnant women had lower IgG1:IgG3 ratios and neutralization but increased antibody-dependent NK cell cytokine production and neutrophil phagocytosis, especially against novel variants. Pregnancy increased memory CD4+ T cells, IFNγ production, monofunctional dominance, and fatty acid oxidation. Pregnancy may reduce the breadth, composition, and magnitude of humoral and cellular immunity, particularly in response to novel variants.