背景:对于一些疫苗可预防的疾病,对疫苗接种的免疫反应因怀孕状态而改变。妊娠对SARS-CoV-2疫苗反应的影响尚不清楚。
目的:我们试图表征峰值和纵向抗S免疫球蛋白G,免疫球蛋白M,和免疫球蛋白A对基于信使RNA的SARS-CoV-2疫苗在孕妇中的反应,并与未怀孕的人进行比较,生育年龄的人。
方法:我们在接受SARS-CoV-2信使RNA疫苗接种的孕妇和非孕妇中进行了两项平行的前瞻性队列研究。在第一次和第二次疫苗接种时收集血液,第二次给药后2周,并在疫苗接种开始后41.7周进行连续纵向随访。抗S免疫球蛋白M,免疫球蛋白G,和免疫球蛋白A通过酶联免疫吸附试验进行分析。我们排除了以前有SARS-CoV-2感染证据的病史或存在抗核衣壳抗体的人。此外,对于这项研究,我们没有包括在研究期间接受第三剂量疫苗或加强剂量疫苗的个体.我们还排除了在分娩时未完全接种疫苗的孕妇(在接受第二次疫苗剂量后14天)和在研究过程中怀孕的非孕妇。我们使用Spearman相关性研究了疫苗接种时胎龄对抗S反应的影响。我们使用Mann-WhitneyU检验比较了孕妇和非孕妇之间的抗S抗体峰值反应。我们使用局部加权散点图平滑法可视化并研究了纵向抗S抗体反应,Mann-WhitneyU测试,和混合方差分析。
结果:本分析包括53名孕妇和21名非孕妇的数据。孕妇和非孕妇的中位年龄(四分位距)为35.0(33.3-37.8)岁和36.0(33.0-41.0)岁,分别。六名(11.3%)参与者在孕早期开始接种疫苗,妊娠中期23例(43.3%),妊娠晚期24例(45.3%),分娩时的中位胎龄为39.6周(39.0-40.0周)。在妊娠和非妊娠队列中,从开始接种疫苗到最后一次采集血液样本的中位(四分位范围)随访时间为25.9(11.9)周和28.9(12.9)周。分别。在孕妇中,抗S免疫球蛋白G,免疫球蛋白A,免疫球蛋白M反应与疫苗接种时的胎龄无关(P均>.05)。第二次给药后2周的抗S免疫球蛋白G应答在孕妇和非孕妇之间没有统计学差异(P>.05)。然而,第二次给药后2周抗S免疫球蛋白M和免疫球蛋白A应答在非妊娠患者中显著增高(两者P<.001).疫苗接种后6至8个月,孕妇和非孕妇的抗S免疫球蛋白G和免疫球蛋白M水平下降到第二剂量抗体水平后2周峰值的可比比例(免疫球蛋白GP=.77;免疫球蛋白MP=.51)。相比之下,疫苗接种后6至8个月的免疫球蛋白A水平下降到统计学上显著高于第二剂量抗体水平后2周的峰值比例与非孕妇相比(P=.002)。母体抗S免疫球蛋白G水平与脐带抗S免疫球蛋白G水平密切相关(R=0.8,P<.001)。
结论:抗S免疫球蛋白A,免疫球蛋白M,和免疫球蛋白G对SARS-CoV-2疫苗接种的反应在怀孕期间与疫苗启动的胎龄无关。在孕妇和非孕妇之间,免疫球蛋白G反应的维持是相当的。孕妇和非孕妇之间免疫球蛋白M和免疫球蛋白A的差异峰值反应以及抗S免疫球蛋白A的差异下降需要进一步研究。
For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear.
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.
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 longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals 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.
Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant 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 vaccination 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, immunoglobulin A, and immunoglobulin M responses were not associated with gestational 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 second 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 nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, 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).
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 nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.