麻省理工学院-哈佛大学的Galit Alter研究组与威尔康奈尔医学中心的Laura E. Riley研究组合作发现，Fc区域的多糖修饰能够调控抗体的胎盘转运。这一研究成果发表在2019年6月27日出版的国际著名学术期刊《细胞》上。

尽管疫苗在全世界范围内取得成功，但新生儿仍然容易受到感染。新生儿的疫苗接种受到多种方式的阻碍，这包括母源抗体介导的免疫反应阻碍、新生儿对抗体的免疫耐受以及新生儿免疫系统的不成熟。因此，母亲的产前免疫旨在通过抗体转运至胎儿来提高新生儿免疫力。然而，目前的证据表明，抗体无法有效地通过胎盘进行转运。

为解决这一难题，研究人员通过系统性地分析血清样本来寻找与抗体转运相关的Fc特征。新生儿与母体的Fc谱并不同，能转运过胎盘的抗体是那些偏好于激活自然杀伤细胞的抗体。这种选择性的转运与抗体Fc区域的二半乳糖化修饰有关，被修饰后的Fc通过选择性地与FcRn和FCGR3A结合来实现抗体转运，进一步这些抗体能够高效地激活胎儿出生时的先天性免疫细胞。因此，这项研究表明，在研发下一代母体疫苗中设计糖基化修饰的抗体可为新生儿提供最有效的免疫防御。

附：英文原文

Title: Fc Glycan-Mediated Regulation of Placental Antibody Transfer

Author: Madeleine F. Jennewein, Ilona Goldfarb, Sepideh Dolatshahi, Arthur Y. Kim, Laura E. Riley, Galit Alter

Issue&Volume: Jun 27, 2019 Volume 178Issue 1

Abstract: Despite the worldwide success of vaccination, newborns remain vulnerable to infections. While neonatal vaccination has been hampered by maternal antibody-mediated dampening of immune responses, enhanced regulatory and tolerogenic mechanisms, and immune system immaturity, maternal pre-natal immunization aims to boost neonatal immunity via antibody transfer to the fetus. However, emerging data suggest that antibodies are not transferred equally across the placenta. To understand this, we used systems serology to define Fc features associated with antibody transfer. The Fc-profile of neonatal and maternal antibodies differed, skewed toward natural killer (NK) cell-activating antibodies. This selective transfer was linked to digalactosylated Fc-glycans that selectively bind FcRn and FCGR3A, resulting in transfer of antibodies able to efficiently leverage innate immune cells present at birth. Given emerging data that vaccination may direct antibody glycosylation, our study provides insights for the development of next-generation maternal vaccines designed to elicit antibodies that will most effectively aid neonates.

DOI: https://doi.org/10.1016/j.cell.2019.05.044

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30615-4