krn-7000 has been researched along with Hepatitis-B* in 2 studies
1 trial(s) available for krn-7000 and Hepatitis-B
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Efficacy of ABX196, a new NKT agonist, in prophylactic human vaccination.
We have assessed the immune-regulatory and adjuvant activities of a synthetic glycolipid, ABX196, a novel analog of the parental compound α-GalCer. As expected, ABX196 demonstrated a measurable and significant adjuvant effect in mice and monkeys with no appreciable toxicity at the doses used to promote immune responses. We performed a phase I/II dose escalation study of ABX196 in healthy volunteers, with the objectives to evaluate its safety profile, as well as its ability to be utilized as an adjuvant in the context of a prophylactic vaccine against hepatitis B. ABX196 was administered at three doses: 0.2, 0.4, and 2.0μg, in 44 subjects. In all the individuals injected with ABX196, peripheral blood NKT cells displayed hallmarks of activation, and 45% of them had measurable circulating IFN-γ 24h after the first administration. More importantly, the addition of ABX196 to the very poorly immunogenic HBs antigen resulted in protective anti-HBs antibody responses in majority of patients, demonstrating the adjuvant properties of ABX196 in human. Further analysis of the cohort of subjects receiving ABX196 with HBs antigen also indicates that a single injection appears sufficient to provide protection. A limited set of adverse events linked to the systemic delivery of ABX196 and access to the liver, is discussed in the context of formulation and the need to limit transport of ABX196 to secondary lymphoid tissues for maximal efficacy (Eudra-CT 2012-001566-15). Topics: Adjuvants, Immunologic; Adult; Animals; Double-Blind Method; Galactosylceramides; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Humans; Interferon-gamma; Macaca fascicularis; Male; Mice; Molecular Structure; Natural Killer T-Cells | 2014 |
1 other study(ies) available for krn-7000 and Hepatitis-B
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Role of Valpha14+ NKT cells in the development of Hepatitis B virus-specific CTL: activation of Valpha14+ NKT cells promotes the breakage of CTL tolerance.
CTLs are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (alpha-GalCer), a ligand for Valpha14-positive NKT cells, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or alpha-GalCer alone failed to induce HBsAg-specific CTLs, but they were induced by co-administration of both compounds. Furthermore, by limiting dilution analysis, we confirmed the existence of HBsAg-specific CTL precursors in the HBsAg transgenic mice immunized with HBsAg and alpha-GalCer. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40-CD40L interaction mediate the enhancement of CTL induction caused by alpha-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection. Topics: Animals; Antigens, Viral; Cell Line, Tumor; Cells, Cultured; Galactosylceramides; Genes, T-Cell Receptor alpha; Hepatitis B; Hepatitis B virus; Immune Tolerance; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Natural Killer T-Cells; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic | 2008 |