Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cell Rep. 2022 May 3;39(5):110772. doi: 10.1016/j.celrep.2022.110772.
Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the possibility that LPCs contribute to BCG immunogenicity. Analysis of an independent newborn cohort from The Gambia demonstrates shared vaccine-induced metabolites, such as phospholipids and sphingolipids. BCG-induced changes to the plasma lipidome and LPCs may contribute to its immunogenicity and inform the development of early life vaccines.
疫苗的研发通常缺乏对其分子作用的深入了解。尽管系统疫苗学能够对作用机制进行特征描述，但这些工具尚未应用于婴儿，而婴儿感染风险高，接种的疫苗也最多。卡介苗（BCG）通过尚未完全明确的机制，为婴儿预防全身性结核病（TB）和与 TB 无关的感染提供保护。我们采用基于质谱的血浆代谢组学方法，对几内亚比绍体内和美国体外的 BCG 诱导的婴儿反应进行了分析。BCG 诱导的溶血磷脂酰胆碱（LPC）与体外 TLR 激动剂和纯化蛋白衍生物（PPD，分枝杆菌抗原）诱导的血液细胞因子产生相关，这提示 LPC 可能有助于 BCG 的免疫原性。对来自冈比亚的一个独立新生儿队列的分析表明，存在共享的疫苗诱导代谢物，如磷脂和神经鞘脂。BCG 诱导的血浆脂质组和 LPC 的变化可能有助于其免疫原性，并为早期生命疫苗的开发提供信息。
