Atyeo Caroline, DeRiso Elizabeth A, Davis Christine, Bordt Evan A, DeGuzman Rose M, Shook Lydia L, Yonker Lael M, Fasano Alessio, Akinwunmi Babatunde, Lauffenburger Douglas A, Elovitz Michal A, Gray Kathryn J, Edlow Andrea G, Alter Galit
bioRxiv. 2021 Apr 5:2021.04.04.438404. doi: 10.1101/2021.04.04.438404.
Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of the fetal graft. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against foreign invaders both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe COVID-19 disease. Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable, albeit slightly lower, between pregnant and lactating women, compared to non-pregnant controls. Among pregnant women, we found higher antibody titers and functions in those vaccinated with the Moderna vaccine. FcR-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data point to an immune resistance to generate highly inflammatory antibodies during pregnancy and lactation, and a critical need to follow prime/boost timelines in this vulnerable population to ensure full immunity is attained.
在整个孕期会发生显著的免疫变化，以使母亲产生免疫耐受并允许胎儿移植物生长。然而，还会出现额外的局部和全身免疫适应，使母体免疫系统在孕期和产后通过哺乳继续保护母婴免受外来入侵者的侵害。这种耐受性和免疫的精细平衡，以及生理和激素变化，导致孕妇对特定感染的易感性增加，包括更严重的新冠病毒疾病。这些变化是否也会使孕妇对疫苗接种反应降低或诱导对疫苗接种的免疫反应改变，目前仍不完全清楚。为了全面定义孕期和哺乳期疫苗反应的潜在变化，我们深入分析了一组孕妇、哺乳期妇女和年龄匹配的非孕妇对照的体液疫苗反应。与非孕妇对照相比，孕妇和哺乳期妇女的疫苗特异性滴度相当，尽管略低。在孕妇中，我们发现接种Moderna疫苗的孕妇抗体滴度和功能更高。与非孕妇相比，孕妇和哺乳期妇女的FcR结合和抗体效应功能诱导动力学延迟。抗体增强导致母乳中FcR结合滴度升高。这些数据表明，在孕期和哺乳期存在产生高炎症性抗体的免疫抗性，并且在这个脆弱人群中迫切需要遵循初次/加强接种时间表以确保获得完全免疫。
