Longitudinal antibody response kinetics following SARS-CoV-2 mRNA vaccination in pregnant and non-pregnant persons.
Academic Article
Overview
abstract
BACKGROUND: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by the pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. OBJECTIVE: We sought to characterize the peak and longitudinal anti-S IgG, IgM, and IgA responses to messenger RNA (mRNA)-based SARS-CoV-2 vaccination in pregnant persons and compare it to that in non-pregnant, reproductive-aged persons. STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and non-pregnant persons who received SARS-CoV-2 mRNA vaccinations. Blood was collected at the time of first (t0) and second (t1) vaccine doses, 2 weeks post second dose (t2), and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S IgM, IgG, and IgA were analyzed by ELISA. We excluded those with prior evidence of SARS-CoV-2 infection by history or presence of anti-nucleocapsid antibodies. Additionally, for this study, we did not include individuals with receipt of a third or booster vaccine dose during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dose) by time of delivery and non-pregnant persons who became pregnant throughout the course of the study. We studied the effect of gestational age (GA) at vaccination on anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and non-pregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using LOESS, Mann-Whitney U test, and Mixed Anova test. RESULTS: Data from 53 pregnant persons and 21 non-pregnant persons were included in this analysis. The median (interquartile range, IQR) age of the pregnant and non-pregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) initiated vaccination in the second trimester, and 24 (45.3%) initiated vaccination in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (IQR) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and non-pregnant cohort, respectively. Among pregnant persons, anti-S IgG, IgA, and IgM responses were not associated with GA at vaccine initiation (all p>0.05). The anti-S IgG response at t2 was not statistically different between pregnant and non-pregnant persons (p>0.05); however, the anti-S IgM and IgA responses at t2 were significantly higher in non-pregnant persons (p<0.001 for both) . Anti-S IgG and IgM levels 6-8 months after vaccine initiation fell to comparable proportions of the peak t2 antibody levels between pregnant and non-pregnant persons (IgG p=0.77; IgM p=0.51). In contrast, IgA levels 6-8 months after vaccine initiation fell to statistically significantly higher proportions of peak t2 antibody levels in pregnant compared to non-pregnant persons (p=.002). Maternal anti-S IgG levels were strongly correlated with umbilical cord anti-S IgG levels (R=0.8, p < 0.001). CONCLUSIONS: The anti-S IgA, IgM, and IgG response to SARS-CoV-2 vaccination in pregnancy is independent of GA of vaccine initiation. Maintenance of the IgG response is comparable between pregnant and non-pregnant persons. The differential peak response of IgM and IgA, as well as the differential decline of anti-S IgA between pregnant and non-pregnant persons requires further investigation.
