Abstract
We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLPAs).The HIV-VLPAs induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells.In the present manuscript, the effects of the baculovirus-expressed HIV-VLPAs on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLPA stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation.The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLPAs at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers.
Highlights
Virus-like particles (VLPs) represent a peculiar form of teins which show the ability to self-assemble into highly
Baculovirus-HIV-VLP induces a maturation phenotype of Dendritic cells (DCs) Immature monocyte-derived dendritic cells (MDDCs) were obtained from three independent donors and, after 6 days of culture in IL-4- and GM-CSFenrichment medium, were incubated with 5 μg/ml of baculovirus-expressed HIV-VLPs or 1μg/ml of LPS
The level of cytokines involved in the Th1/ Th2 polarization was assessed in the supernatant of MDDCs loaded with HIV-VLPs or LPS
Summary
Virus-like particles (VLPs) represent a peculiar form of teins which show the ability to self-assemble into highly (page number not for citation purposes). VLPs can be employed to deliver additional antigenic structures, such as whole proteins or specific individual epitopes and have been shown to generally induce more effective humoral and cellular immune response than their soluble counterparts [3]. Considering all these properties, VLPs represent a highly attractive vaccine approach and have been produced from a broad spectrum of enveloped and non-enveloped viruses, regardless of whether the particle structure is based on single or multiple capsid proteins [4]. The intra-peritoneal and the intra-nasal administrations of HIV-VLPAs induce in mice an antibody response at systemic as well as local (vaginal and intestinal) level [9]
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