CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
Year: 2022
Type: article
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.
Source: Nature Communications
Authors: 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, Peter Andersen, Barney S. Graham, Hanno Steen, Dennis Christensen, Ofer Levy
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, Bill and Melinda Gates Foundation, Brigham and Women's Hospital, Boston Children's Hospital, National Institutes of Health, DHHS Office of the Secretary, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1836308875, G1887288462, G2277489774, Pediatric Infectious Diseases Research Training, G2814664472, Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity, Dissecting the mechanism of age-specific adjuvant synergy in vitro and in vivo, G6100960918, Children's Hospital Boston - to apply unique human in vitro platforms to characterize immune responses of adjuvants that are being developed for Global Health vaccines, G6879041785, G8312510772
OpenAlex ID: W4289520173