Alpha-kinase 1 (ALPK1) agonist DF-006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B.

BACKGROUND AND AIMS: In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha-kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF-κB pathway and stimulates innate immunity. Here we characterized the preclinical anti-HBV efficacy of DF-006, an orally active agonist of ALPK1 currently in clinical development for CHB. APPROACH AND RESULTS: In adeno-associated virus (AAV)-HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF-006. In the mouse models, DF-006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 µg/kg, 1 µg/kg, and 5 µg/kg, respectively. DF-006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF-006 also showed anti-HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF-006, there was upregulation of NF-κB-targeted genes that are involved in innate immunity. CONCLUSION: DF-006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF-006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti-HBV efficacy by DF-006.

Haptoglobin Phenotypes and Susceptibility to Schistosoma Parasites Infection in Central Sudan.

Haptoglobin (Hp) is an acute phase protein that binds the free hemoglobin (Hb), thus preventing iron loss and renal damage. Hp also has antioxidative and immunomodulatory properties. Three Hp phenotypes have been identified in human: Hp1-1, Hp2-1, and Hp2-2. Hp polymorphisms have been related to susceptibility of various diseases. In this study, we aimed to assess the possible association of Hp phenotypes polymorphism to Schistosoma parasites infection in central Sudan. We have investigated the Hp phenotypes polymorphism distribution in the serum of 125 (93 S. mansoni, 13 S. haematobium and 19 infected with both "co-infection") parasitologically confirmed infected individuals and 208 healthy individuals served as control. Hp phenotypes have been determined by polyacrylamide gel electrophoresis followed by benzidine staining. Our study revealed that Hp1-1 percentage frequency was significantly higher in infected individuals than healthy control individuals 51% and 26% respectively. Our data suggest that Hp1-1 phenotype may upsurge the susceptibility to Schistosoma parasites infection in central Sudan.

Detection of schistosomiasis antibodies in urine patients as a promising diagnostic maker.

OBJECTIVE: To determine secreted antischistosoma antibodies in urine and to discern the epidemiological situation of schistosomiasis in the agricultural field labourers'camps city in the Gezira State-central Sudan. METHODS: Total of 66 urine and 66 serum paired samples were collected from those who confirmed parasitologically positive and negative with schistosomiasis from the two camps. Samples were tested using ELISA technique to measure and compare the immunoglobulin G (IgG) levels in serum and urine samples of schistosomiasis patients. RESULTS: The overall prevalence of S. mansoni and S. haematobium was 53.8% and 15.4%, while the intensity were (2.04 GMEC) and (0.9 GMEC) respectively. The relative percentage of positive IgG individulas in urine was 92.40% where as 96.97% in serum. Statistically no significant difference between the IgG levels in serum and urine samples was observed. CONCLUSIONS: This study shows that the detection of secreted IgG antibodies in urine can substitute serum for diagnosis of schistosomiasis.