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

Author

Listed:
  • Simon D. Haren

    (Boston Children’s Hospital
    Harvard Medical School)

  • Gabriel K. Pedersen

    (Statens Serum Institut)

  • Azad Kumar

    (National Institutes of Health)

  • Tracy J. Ruckwardt

    (National Institutes of Health)

  • Syed Moin

    (National Institutes of Health)

  • Ian N. Moore

    (National Institutes of Health)

  • Mahnaz Minai

    (National Institutes of Health)

  • Mark Liu

    (Boston Children’s Hospital)

  • Jensen Pak

    (Boston Children’s Hospital)

  • Francesco Borriello

    (Boston Children’s Hospital
    Harvard Medical School
    University of Naples Federico II
    Generate Biomedicines)

  • Simon Doss-Gollin

    (Boston Children’s Hospital)

  • Elisabeth M. S. Beijnen

    (Boston Children’s Hospital)

  • Saima Ahmed

    (Boston Children’s Hospital and Harvard Medical School)

  • Michaela Helmel

    (Boston Children’s Hospital and Harvard Medical School)

  • Peter Andersen

    (Statens Serum Institut
    University of Copenhagen)

  • Barney S. Graham

    (National Institutes of Health)

  • Hanno Steen

    (Boston Children’s Hospital
    Boston Children’s Hospital and Harvard Medical School)

  • Dennis Christensen

    (Statens Serum Institut)

  • Ofer Levy

    (Boston Children’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

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.

Suggested Citation

  • Simon D. 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. Bei, 2022. "CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31709-2
    DOI: 10.1038/s41467-022-31709-2
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