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.

由于产生体液免疫反应的能力有限，婴儿的耐受性免疫表型容易受到感染，这阻碍了新生儿疫苗接种的成功。IgG 经胎盘从母亲转移到胎儿在出生后的最初几周提供了重要的保护，母体免疫接种最近已作为一项公共卫生策略实施，以保护新生儿免受严重感染。尽管取得了早期的成功，但目前的母体疫苗并不能在具有不同胎龄、胎盘和母体免疫特征的妊娠中提供类似的保护，并且它们没有考虑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和研究怀孕人类 IgG 转移的纵向动力学的安全挑战，母体疫苗的合理设计进展受到阻碍。或者，计算机机制模型是解开调节胎盘抗体转移过程的逻辑框架。本综述通过机制建模镜头综合了当前文献，以确定抗体转移的胎盘和母体调节因子、它们的临床协变量和知识差距，以指导未来的研究。我们还描述了使用集成建模和实验方法理性设计疫苗以应对现有和新出现的新生儿病原体威胁的机会。