Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

Immunological adjuvants that induce T cell-mediate immunity (TCMI) with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL) and CpGs oligodeoxynucleotides (CpG ODNs) derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR)4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL), lipopeptide (Pam3Cys), and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4+ T and CD8+ T cell responses. In particular, both GIPLs (GTH, and GY) and CpG ODNs (B344, B297 and B128) derived from T. cruzi elicited interferon-gamma (IFN-γ) production by CD4+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception). The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4+ T and CD8+ T cell responses elicited by a specific immunological adjuvant

The structure of a complex glycosylphosphatidyl inositol-anchored glucoxylan from the kinetoplastid protozoan Leptomonas samueli.

The structure of a glycosylphosphatidyl inositol-anchored glucoxylan (GPI-glucoxylan) synthesized by the monogenetic trypanosomatid Leptomonas samueli has been determined. The glucoxylan is anchored to the membrane by phytoceramide and an oligosaccharide core, the structure of which is identical to glycoinositolphospholipids (GIPLs) expressed by this protozoan. The glucoxylan chain is linear, containing -->4Glcalpha1-->, -->4Xylbeta1--> and -->3Xylbeta1--> residues. A well defined sequence heterogeneity was analysed in terms of a series of overlapping trisaccharide substructures. A proportion of the chains are capped with a GlcAalpha1-->3Glcalpha1--> sequence. While an average GlcA-capped chain contained 10 Glc and 16 Xyl residues, uncapped chains have a higher molecular mass with an average of 30 Glc and 50 Xyl per chain. We propose a mode of biosynthesis based on the observed structural heterogeneity

The structure of a complex glycosylphosphatidyl inositol-anchored glucoxylan from the kinetoplastid protozoan Leptomonas samueli.

The structure of a glycosylphosphatidyl inositol-anchored glucoxylan (GPI-glucoxylan) synthesized by the monogenetic trypanosomatid Leptomonas samueli has been determined. The glucoxylan is anchored to the membrane by phytoceramide and an oligosaccharide core, the structure of which is identical to glycoinositolphospholipids (GIPLs) expressed by this protozoan. The glucoxylan chain is linear, containing -->4Glcalpha1-->, -->4Xylbeta1--> and -->3Xylbeta1--> residues. A well defined sequence heterogeneity was analysed in terms of a series of overlapping trisaccharide substructures. A proportion of the chains are capped with a GlcAalpha1-->3Glcalpha1--> sequence. While an average GlcA-capped chain contained 10 Glc and 16 Xyl residues, uncapped chains have a higher molecular mass with an average of 30 Glc and 50 Xyl per chain. We propose a mode of biosynthesis based on the observed structural heterogeneity