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

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. Beijnen, Saima Ahmed, Michaela Helmel, Peter Andersen, Barney S. Graham, Hanno Steen, Dennis Christensen and Ofer Levy
Additional contact information
Simon D. Haren: Boston Children’s Hospital
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
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
Barney S. Graham: National Institutes of Health
Hanno Steen: Boston Children’s Hospital
Dennis Christensen: Statens Serum Institut
Ofer Levy: Boston Children’s Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31709-2

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DOI: 10.1038/s41467-022-31709-2

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