Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Virginia, Charlottesville, VA, USA.
Carter Immunology Center, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Nat Immunol. 2024 Nov;25(11):2024-2036. doi: 10.1038/s41590-024-01971-1. Epub 2024 Oct 8.
Infants are vulnerable to infections owing to a limited ability to mount a humoral immune response and their tolerogenic immune phenotype, which has impeded the success of newborn vaccination. Transplacental transfer of IgG from mother to fetus provides crucial protection in the first weeks of life, and maternal immunization has recently been implemented as a public health strategy to protect newborns against serious infections. Despite their early success, current maternal vaccines do not provide comparable protection across pregnancies with varying gestational lengths and placental and maternal immune features, and they do not account for the dynamic interplay between the maternal immune response and placental transfer. Moreover, progress toward the rational design of maternal vaccines has been hindered by inadequacies of existing experimental models and safety challenges of investigating longitudinal dynamics of IgG transfer in pregnant humans. Alternatively, in silico mechanistic models are a logical framework to disentangle the processes regulating placental antibody transfer. This Review synthesizes current literature through a mechanistic modeling lens to identify placental and maternal regulators of antibody transfer, their clinical covariates, and knowledge gaps to guide future research. We also describe opportunities to use integrated modeling and experimental approaches toward the rational design of vaccines against existing and emerging neonatal pathogen threats.
婴儿由于体液免疫反应能力有限和耐受免疫表型，容易受到感染，这阻碍了新生儿疫苗接种的成功。母体 IgG 通过胎盘向胎儿的转移为生命的最初几周提供了至关重要的保护，最近已将母体免疫接种作为一种公共卫生策略来保护新生儿免受严重感染。尽管取得了早期成功，但目前的母体疫苗在不同妊娠周期、胎盘和母体免疫特征方面并不能提供可比的保护，而且它们也没有考虑到母体免疫反应和胎盘转移之间的动态相互作用。此外，由于现有实验模型的不足以及在孕妇中研究 IgG 转移的纵向动态的安全性挑战，母体疫苗的合理设计进展受到阻碍。此外，基于机制的计算模型是一种逻辑框架，可以分解调节胎盘抗体转移的过程。这篇综述通过机制建模的视角综合了当前文献，以确定调节抗体转移的胎盘和母体调节剂、它们的临床协变量以及知识空白，以指导未来的研究。我们还描述了利用综合建模和实验方法来合理设计针对现有和新兴新生儿病原体威胁的疫苗的机会。
