A novel Lactococcus lactis antigen delivery system induces activation and maturation of neonatal dendritic cells and T cell stimulation. (36.22)

Abstract

Abstract 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 mucosally in adult mice. To assess their capacity to activate the neonatal immune system, DC and macrophages derived from newborn mice were cultured in the presence of GEM particles. Adult-derived DC were included as controls. We showed that GEM particles induced upregulation of activation and maturation markers (CD80, CD86, CD40, MHCII) in neonatal DC and macrophages. Similar experiments were performed with human DC; GEM particle treatment also increased expression of activation and 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 cell populations, and likely to enhance in vivo immune responses in neonates.