Comparative immunogenicity of COVID-19 vaccination in pregnant and non-pregnant women: a real-world cohort study.

BACKGROUND

Pregnant individuals are at increased risk of severe COVID-19-related morbidity and adverse obstetric outcomes, highlighting the importance of effective vaccination. Although COVID-19 vaccine safety during pregnancy is well established, real-world evidence on vaccine-induced humoral immunity remains limited. This study compared neutralizing antibody responses after COVID-19 vaccination in pregnant and non-pregnant women and evaluated the effects of vaccine dose number, platform, and timing during pregnancy.

METHODS

This retrospective cohort study included 171 vaccinated women of reproductive age, comprising 95 pregnant and 76 non-pregnant participants. Neutralizing antibody titers were measured using a surrogate virus neutralization test. Vaccine platforms included mRNA vaccines (BNT162b2, Pfizer-BioNTech), inactivated vaccines (CoronaVac, Sinovac), and a small number of heterologous regimens. Antibody levels were compared using the Mann-Whitney U test. Associations between antibody titers and vaccine dose number, age, gestational age, and trimester were assessed using Spearman correlation analyses and Jonckheere-Terpstra trend tests.

RESULTS

Pregnant women had significantly lower neutralizing antibody titers than non-pregnant controls (median 5.62 vs. 16.25 AU/mL; p = 0.008) and were less likely to reach the assay's upper detection limit (≥30 AU/mL: 18.9% vs. 43.4%). Although the categorical distribution of vaccine dose counts was broadly similar between groups (χ 2 p = 0.098), the mean number of doses was significantly lower among pregnant women (1.93 ± 0.72 vs. 2.32 ± 1.02; p = 0.011), reflecting differences in cumulative vaccine exposure at higher dose levels. Antibody titers were strongly associated with vaccine dose number overall (ρ = 0.341, p < 0.001) and in both pregnant and non-pregnant women. When stratified by dose category, antibody titers did not differ by pregnancy status. Gestational age and trimester were not independently associated with antibody levels, although the dose-response relationship was strongest in second-trimester vaccination. In unadjusted comparisons, mRNA vaccines were associated with numerically higher titers than inactivated vaccines (median 11.30 vs. 7.72 AU/mL; p = 0.165). mRNA platform was also independently associated with higher titers in multivariable analysis (β = 0.721, p = 0.030); this finding should be interpreted cautiously given the small inactivated-vaccine subgroup (n = 18).

CONCLUSION

COVID-19 vaccination elicits robust neutralizing antibody responses in pregnant women, with overall humoral responsiveness preserved despite quantitative differences in antibody magnitude. Lower antibody levels are predominantly explained by differences in cumulative vaccine exposure rather than pregnancy-related immune impairment, although a residual independent association of pregnancy cannot be fully excluded. Completing recommended vaccine schedules is essential to optimize maternal and neonatal protection.