tretinoin and aluminum-sulfate

Diarrheal infectious diseases represent a major cause of global morbidity and mortality. There is an urgent need for vaccines against diarrheal pathogens, especially parasites. Modern subunit vaccines rely on combining a highly purified antigen with an adjuvant to increase their efficacy. In the present study, we evaluated the ability of a nanoliposome adjuvant system to trigger a strong mucosal immune response to the Entamoeba histolytica Gal/GalNAc lectin LecA antigen. CBA/J mice were immunized with alum, emulsion or liposome based formulations containing synthetic TLR agonists. A liposome formulation containing TLR4 and TLR7/8 agonists was selected based on its ability to generate intestinal IgA, plasma IgG2a/IgG1, IFN-γ and IL-17A. Immunization with a mucosal prime followed by a parenteral boost generated a high mucosal IgA response that inhibited adherence of parasites to mammalian cells. Inclusion of the immune potentiator all-trans retinoic acid in the regimen further improved the mucosal IgA response. Immunization protected from infection with up to 55% efficacy. Our results show that a nanoliposome delivery system containing TLR agonists is a promising prospect for the development of vaccines against enteric pathogens, especially when a multifaceted immune response is desired.

Topics: Adjuvants, Immunologic; Alum Compounds; Animals; Antibodies, Protozoan; Antigens, Protozoan; Entamoeba histolytica; Entamoebiasis; Immunity, Mucosal; Immunization; Interferon-gamma; Interleukin-17; Lectins; Lipopolysaccharides; Liposomes; Membrane Glycoproteins; Mice; Mice, Inbred CBA; Oligodeoxyribonucleotides; Polysorbates; Protozoan Vaccines; RNA; Squalene; Toll-Like Receptor 3; Toll-Like Receptor 7; Toll-Like Receptor 8; Tretinoin; Vaccines, Subunit

The effects of the thyroid hormone triiodothyronine (T3), nerve growth factor (NGF) and stress (exposure to heat or aluminum sulfate) on growth, development and ageing of human neuroblastoma cells were studied in vitro. Differentiation of cells using retinoic acid and NGF inhibits cell growth and proliferation; simultaneously, it promotes acquisition of neuronal phenotype, down-regulation of T3 receptors, and an increase in catecholaminergic tyrosine hydroxylase activity and microtubule assembly. The actions of T3 on neuronal differentiation resemble those of NGF and suggest the existence of NGF-T3 interactions. Exposure to stress inhibits cell growth and proliferation, increases immunoreactivity to the microtubule-assembling protein tau (which occurs in paired filaments of neurofibrillary tangles in the aged human brain), and facilitates formation of tau-ubiquitin complexes (which also occur in the aged brain). Stress does not prevent the inhibition of cell proliferation by high doses of T3; however, T3 doses that are equivalent to physiological levels reduce stress-induced inhibition of growth. Previous studies have shown that stress may also induce in these cells facsimile lesions of normal and abnormal ageing, such as accumulation of lipofuscin pigments, formation of paired helical filaments and increased immunoreactivity to tau, beta-amyloid proteins, and ubiquitin. These lesions may represent cellular and molecular manifestations of increased vulnerability and susceptibility to genetic and extrinsic factors (e.g. hormones and environmental influences) with ageing. It is proposed that neuroblastoma cells may serve as a model to study mechanisms of neuronal ageing and to identify agents and conditions capable of preventing, delaying or reducing metabolic abnormalities leading to age-associated disorders.

Topics: Aging; Alum Compounds; Brain; Cell Differentiation; Cell Division; Cellular Senescence; DNA, Neoplasm; Hot Temperature; Humans; Models, Neurological; Nerve Growth Factors; Neuroblastoma; Receptors, Thyroid Hormone; tau Proteins; Tretinoin; Triiodothyronine; Tumor Cells, Cultured; Ubiquitins