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

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.

A protective, single-visit TB vaccination regimen by co-administration of a subunit vaccine with BCG

“…Therefore, an ideal TB vaccination regimen would consist of a single administration for maximum coverage at minimal cost. Several studies support the notion that a single-dose vaccination regimen has the potential to be durably efficacious against other diseases [6][7][8][9][10][11] .…”

Molecular Determinants of the Early Life Immune Response to COVID-19 Infection and Immunization

“…It is evident that adaptive immune responses significantly change as age increases. Together with factors affecting innate immunity such as NK cell senescence and functionally distinct PRR responses as described previously [ 16 , 17 , 23 , 37 , 133 , 134 , 135 , 136 , 137 ], generating similar immune responses in adults and children seems challenging. Maturation of the innate and adaptive immune system in adults may partly explain the more favorable prognosis in children after an infection with COVID-19.…”

“…The resulting impairment in early life to promote T-helper 1 immunity to novel pathogens can prime the immune system of children to the preferential induction of a tolerogenic or sometimes detrimental T-helper 2 response [ 29 , 32 , 33 ]. While these intrinsic features of the developing immune system may have proven disadvantageous in the context of other respiratory viruses such as RSV [ 34 , 35 , 36 , 37 , 38 ], it has been postulated that in the context of SARS-CoV-2 this may contribute to reduced disease burden in this age group [ 11 ]. In addition, investigation into the age-specific differences in pathology and immune response to infection could contribute to improved future vaccine formulations tailored for children.…”

New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus

“… 25 , 42–45 Preclinical research has suggested that this approach could be feasible in the immune system of newborns. 46 , 47 …”

“…25,[42][43][44][45] Preclinical research has suggested that this approach could be feasible in the immune system of newborns. 46,47 Notwithstanding the troubled history of hRSV vaccine development, intense research efforts in the past decades have led to several vaccine candidates in various stages of preclinical and clinical research, including subunit vaccines, 48,49 viral vector vaccines, [50][51][52] DNA-based vaccines, 53,54 and recombinant Mycobacterium bovis Bacillus Calmette-Guérin (BCG)-based vaccines, [55][56][57][58] among others. 48,49,[56][57][58][59][60][61][62][63][64] As with other areas of drug development, current efforts have tapped into the now extensive structural knowledge of hRSV to identify novel pharmacological targets.…”