A single immunization with CAF08 provides newborns with Th1-mediated protection against Respiratory Syncytial Virus infection
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ABSTRACT: Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of T-helper 1 (Th1)‐immunity. Here we describe cationic adjuvant formulation (CAF)-08, a liposomal vaccine formulation tailored to induce Th1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. Quantitative phosphoproteomics applied to human dendritic cells revealed a key role for Protein Kinase C- for enhanced Th1 cytokine production in neonatal dendritic cells and identified signaling events resulting in antigen cross-presentation. In vivo, a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protected newborn mice from RSV infection through induction of antigen-specific CD8+ and Th1 cells. Overall, we describe a novel pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other intracellular pathogens.
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Primary Cell, Blood Cell, Dendritic Cell, Cell Culture
SUBMITTER: Simon van Haren
LAB HEAD: Simon van Haren
PROVIDER: PXD025568 | Pride | 2022-06-14
REPOSITORIES: Pride
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