CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
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CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns. / van Haren, Simon D.; Pedersen, Gabriel K.; Kumar, Azad; Ruckwardt, Tracy J.; Moin, Syed; Moore, Ian N.; Minai, Mahnaz; Liu, Mark; Pak, Jensen; Borriello, Francesco; Doss-Gollin, Simon; Beijnen, Elisabeth M.S.; Ahmed, Saima; Helmel, Michaela; Andersen, Peter; Graham, Barney S.; Steen, Hanno; Christensen, Dennis; Levy, Ofer.
In: Nature Communications, Vol. 13, No. 1, 4234, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
AU - van Haren, Simon D.
AU - Pedersen, Gabriel K.
AU - Kumar, Azad
AU - Ruckwardt, Tracy J.
AU - Moin, Syed
AU - Moore, Ian N.
AU - Minai, Mahnaz
AU - Liu, Mark
AU - Pak, Jensen
AU - Borriello, Francesco
AU - Doss-Gollin, Simon
AU - Beijnen, Elisabeth M.S.
AU - Ahmed, Saima
AU - Helmel, Michaela
AU - Andersen, Peter
AU - Graham, Barney S.
AU - Steen, Hanno
AU - Christensen, Dennis
AU - Levy, Ofer
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-31709-2
DO - 10.1038/s41467-022-31709-2
M3 - Journal article
C2 - 35918315
AN - SCOPUS:85135255578
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4234
ER -
ID: 317091846