Immunogenicity of COVID-19 Vaccines During Pregnancy: A Systematic Review and Comparison of Pregnant Versus Nonpregnant Persons

Abstract

Background: The COVID-19 pandemic induced the rapid deployment of novel vaccines with pregnant persons identified as an at-risk population due to their increased risk of severe outcomes. Limited data on the immunogenicity of COVID-19 vaccines in pregnant persons were available at the time of implementation. To address this data gap, we developed a living systematic review summarizing emerging evidence on vaccine immunogenicity in pregnancy.Methods: Following Cochrane, World Health Organization, and Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we included studies on COVID-19 vaccines during pregnancy. We carried out comprehensive biweekly literature searches from March 2022 to October 2023, covering multiple databases. Study selection, data extraction and risk of bias assessment were conducted by pairs of authors independently. Immunogenicity outcomes, primarily post-vaccination neutralizing or binding antibody concentrations, were analyzed descriptively. Post-vaccination antibody ratios in pregnant versus nonpregnant individuals were calculated for the subset of studies that included nonpregnant comparators.Results: By October 2023, our review encompassed 62 studies predominantly analyzing maternal sera (87%), with limited investigation regarding cord, neonatal and infant sera. Most studies investigated mRNA vaccines (97%) and focused on primary vaccination (82%), with some investigating booster doses (15%). Immunogenicity end points included spike-specific IgG (84%) and neutralizing antibodies (24%), with limited data on T-cell responses (3%). Antibodies were detectable after primary vaccination in most pregnant individuals, with similar or modestly attenuated concentrations compared to nonpregnant individuals (ratios > 0.7 for 5/6 estimates of spike-specific IgG), albeit with modest differences in antibody quality and kinetics. Long-term antibody-waning trajectories were similar between pregnant and nonpregnant individuals for up to 8 months after vaccination.Conclusions: mRNA COVID-19 vaccines induce a robust antibody response during pregnancy comparable (or modestly attenuated) relative to nonpregnant individuals. Immunogenicity data on non-mRNA vaccines are notably underrepresented in the existing literature.