A single immunization with CAF08 provides newborns with Th1-mediated protection against Respiratory Syncytial Virus infection

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.102-102.14
• Main Authors: van Haren, Simon D., Pedersen, Gabriel, Kumar, Azad, Ruckwardt, Tracy, Moin, Syed, Moore, Ian, Minai, Mahnaz, Liu, Mark, Pak, Jensen, Borriello, Francesco, Ahmed, Saima, Helmel, Michaela, Andersen, Peter, Graham, Barney S, Steen, Hanno, Christensen, Dennis, Levy, Ofer
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.206.Supp.102.14

Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of T-helper 1 (Th1)□immunity. Here we describe cationic adjuvant formulation (CAF)-08, a liposomal vaccine formulation tailored to induce Th1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. Quantitative phosphoproteomics applied to human dendritic cells revealed a key role for Protein Kinase C-d for enhanced Th1 cytokine production in neonatal dendritic cells and identified signaling events resulting in antigen cross-presentation. In vivo, a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protected newborn mice from RSV infection through induction of antigen-specific CD8+ and Th1 cells. Overall, we describe a novel pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other intracellular pathogens.