Pregnancy Reduces COVID-19 Vaccine Immunity Against Novel Variants

Pregnant individuals are at heightened risk for severe outcomes from many infectious diseases, including COVID-19. However, they were not included in the initial COVID-19 vaccine clinical trials and current rates of vaccine uptake among pregnant people remain below 15%. We defined 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 vaccine viruses in addition to novel variants. Blood was collected from participants prior to and 3-5 weeks post booster vaccine. Post-vaccination antibodies from pregnant participants were less cross-reactive to non-vaccine antigens, including XBB1.5 and JN.1, than antibodies from non-pregnant females. Antibodies from non-pregnant females showed strong correlations between IgG1 and FcR binding and greater IgG1:IgG3 ratios and live virus neutralization against all variants. In contrast, antibodies from pregnant participants had lower IgG1:IgG3 ratios and neutralization and greater antibody-dependent NK cell cytokine production and neutrophil phagocytosis, particularly against variants. CD4+ T cells from pregnant patients exhibited reduced polyfunctionality, with IFNγ+ monofunctional dominance. In contrast, among non-pregnant participants, CD4+ T cells displayed greater polyfunctionality, with more IL-21+ cells. Pregnancy may reduce the breadth, composition, and magnitude of humoral and cellular immunity, particularly in response to novel variants, highlighting the need for continued vaccination in this at-risk population.