Longitudinal antibody response kinetics following SARS-CoV-2 messenger RNA vaccination in pregnant and nonpregnant persons

BACKGROUND: For some vaccine-preventable diseases, the immu-nologic response to vaccination is altered by a 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 immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons.STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longi-tudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were ana-lyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of anti-nucleocapsid antibodies. In addition, for this study, we did not include indi-viduals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti -S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann -Whitney U test, and mixed analysis of variance test.RESULTS: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the preg-nant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccina-tion in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) 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 nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immuno-globulin A, and immunoglobulin M responses were not associated with ges-tational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post sec-ond dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpreg-nant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In con-trast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). CONCLUSION: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and non-pregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobu-lin A between pregnant and nonpregnant persons requires further investigation.