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

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  • Simon D. van Haren
  • Gabriel K. Pedersen
  • Azad Kumar
  • Tracy J. Ruckwardt
  • Syed Moin
  • Ian N. Moore
  • Mahnaz Minai
  • Mark Liu
  • Jensen Pak
  • Francesco Borriello
  • Simon Doss-Gollin
  • Elisabeth M.S. Beijnen
  • Saima Ahmed
  • Michaela Helmel
  • Andersen, Peter
  • Barney S. Graham
  • Hanno Steen
  • Dennis Christensen
  • Ofer Levy

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.

Original languageEnglish
Article number4234
JournalNature Communications
Volume13
Issue number1
ISSN2041-1723
DOIs
Publication statusPublished - 2022

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© 2022, The Author(s).

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