A novel Lactococcus lactis antigen delivery system induces activation and maturation of neonatal dendritic cells and T cell stimulation.

DITAMO, Y; VAN ROOSMALEN, ML; LEENHOUTS, K; RAMIREZ, K; PASETTI, MF

Florida, USA

Congreso; 13. 94th Annual Meeting of The American Association of Immunologists; 2005

AAI

Neonatal immune responses to vaccine antigens are usually short lived and Th-2 biased. This has been attributed, in part, to the immaturity of neonatal dendritic cells (DC) which lack full capacity for antigen presentation and T cell stimulation.  Effective priming of the neonatal immune system can be achieved when antigens are delivered in the presence of adequate immunostimulatory signals. We investigated the capacity of a novel L. lactis-derived delivery system, designated Gram-positive Enhancer Matrix (GEM) particles, to stimulate neonatal immune cell populations. This system had been shown to enhance immunity to protein antigens when given co-delivered mucosally in adult mice. To assess their capacity to activate neonatal immune system, DC and macrophages derived from newborn mice were cultured in presence of GEM particles. Adult-derived DC were included as controls. We showed that GEM particles induced upregulation of activation/maturation markers (CD 80, CD86, CD40, MHCII) in neonatal DC and macrophages. Similar experiments were performed with human DC; GEM particle treatment also increased expression of activation/ maturation markers of human cord blood as well as adult derived DC and increased allogeneic human T cell stimulation. These results indicate that GEM particles are proficient stimulators of neonatal immune cells, which are likely to lead to enhanced in vivo immune responses in neonates.