Pregnancy reduces COVID-19 vaccine immunity against novel variants of concern 4377

Abstract Description Pregnant people are at risk for severe outcomes from many infections, including COVID-19. Pregnant patients, however, were not included in clinical trials of COVID-19 vaccines and current rates of vaccine uptake are <15% among pregnant people. We aimed to define the serological and cellular responses to COVID-19 mRNA booster (i.e., ancestral and BA.5) vaccines in pregnant compared with non-pregnant females, to understand how pregnancy affects vaccine-induced immunity against vaccine viruses and novel variants of concern (VOC). Blood was collected from participants prior to and 3-5 weeks post booster vaccine. Post-vaccination antibodies from pregnant patients were less cross-reactive to novel VOC (XBB1.5 and JN.1). Antibodies from non-pregnant females showed strong correlations with IgG1 and FcR binding and greater IgG1:IgG3 ratios and live virus neutralization against all variants. In contrast, antibodies from pregnant patients had lower IgG1:IgG3 ratios and neutralization, particularly against VOC. Polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) were elevated in pregnant and undetectable in non-pregnant females, correlating with reduced CD4 T cell polyfunctionality and reduced isotype class switching among pregnant females. These data suggest pregnancy-induced PMN-MDSCs may render reduced breadth of humoral and cellular immunity particularly in response to VOCs and highlight the need for continued vaccination in this at risk and vaccine hesitant population. Funding Sources FDA CERSI U01FD005942 (SLK), NIH NIAID BAA 75N93021C00045 (AP, RR), NIH NCI U54 CA260492 (SLK, ALC) Topic Categories Vaccines and Immunotherapy (VAC)