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CAF08 佐剂使新生鼠单次接种即可预防呼吸道合胞病毒感染。

CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns.

机构信息

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

出版信息

Nat Commun. 2022 Aug 2;13(1):4234. doi: 10.1038/s41467-022-31709-2.

Abstract

Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8 T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens.

摘要

呼吸道合胞病毒是导致儿童发病和死亡的主要原因,部分原因是他们独特的免疫系统,其特征是 Th1 免疫诱导受损。在这里,我们展示了阳离子佐剂制剂 CAF08 的应用,这是一种脂质体制剂,旨在通过协同激活 Toll 样受体 7/8 和 C 型凝集素受体 Mincle,在生命早期诱导 Th1 免疫。我们应用定量磷酸蛋白质组学研究人类树突状细胞,并揭示蛋白激酶 C-δ在增强新生儿树突状细胞产生 Th1 细胞因子中的作用,并确定导致抗原交叉呈递的信号事件。在一项小鼠体内模型研究中,在出生时用 CAF08 佐剂的 RSV 融合前抗原进行单次免疫接种,可以通过诱导抗原特异性 CD8 T 细胞和 Th1 细胞来保护新生小鼠免受 RSV 感染。总的来说,我们描述了一种儿科佐剂制剂,并对其作用机制进行了表征,为开发针对 RSV 和其他呼吸道病毒病原体的生命早期疫苗提供了有希望的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a59/9346114/203a8e7f6dbc/41467_2022_31709_Fig1_HTML.jpg

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