Jennewein Madeleine F, Kosikova Martina, Noelette Francesca J, Radvak Peter, Boudreau Carolyn M, Campbell James D, Chen Wilbur H, Xie Hang, Alter Galit, Pasetti Marcela F
The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
iScience. 2022 Mar 16;25(4):104088. doi: 10.1016/j.isci.2022.104088. eCollection 2022 Apr 15.
Pregnancy represents a unique tolerogenic immune state which may alter susceptibility to infection and vaccine response. Here, we characterized humoral immunity to seasonal influenza vaccine strains in pregnant and non-pregnant women. Although serological responses to influenza remained largely intact during late pregnancy, distinct modifications were observed. Pregnant women had reduced hemagglutinin subtype-1 (H1)- IgG, IgG1, IgG2, and IgG3, hemagglutination inhibition, and group 1 and 2 stem IgG titers. Intriguingly, H1-specific avidity and FcγR1 binding increased, and influenza antibodies had distinct Fc and Fab glycans characterized by increased di-galactosylation and di-sialylation. H1-specific Fc-functionality (i.e. monocyte phagocytosis and complement deposition) was moderately reduced in pregnancy. Multivariate antibody analysis revealed two distinct populations (pregnant vs. non-pregnant) segregated by H1 FcγR1 binding, H1-IgG levels, and Fab and Fc glycosylation. Our results demonstrated a structural and functional modulation of influenza humoral immunity during pregnancy that was antigen-specific and consistent with reduced inflammation and efficient placental transport.
怀孕代表一种独特的免疫耐受状态，这种状态可能会改变感染易感性和疫苗反应。在此，我们对孕妇和非孕妇针对季节性流感疫苗株的体液免疫进行了特征分析。尽管在妊娠晚期对流感的血清学反应基本保持完整，但仍观察到明显的变化。孕妇的血凝素亚型1（H1）-IgG、IgG1、IgG2和IgG3、血凝抑制以及第1组和第2组茎部IgG滴度降低。有趣的是，H1特异性亲和力和FcγR1结合增加，并且流感抗体具有以二半乳糖基化和二唾液酸化增加为特征的独特Fc和Fab聚糖。在妊娠期间，H1特异性Fc功能（即单核细胞吞噬作用和补体沉积）中度降低。多变量抗体分析显示，根据H1 FcγR1结合、H1-IgG水平以及Fab和Fc糖基化，可将两个不同群体（孕妇与非孕妇）区分开来。我们的结果表明，妊娠期间流感体液免疫存在结构和功能调节，这种调节具有抗原特异性，并且与炎症减轻和胎盘有效转运一致。
