February 2018

Monthly Archive

Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization…

Posted by on 13 Feb 2018 | Tagged as: Hepatitis B Alternative Medicine

Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi. Pediatr Infect Dis J. 2018 Feb 09;: Authors: Witte D, Cunliffe NA, Turner AM, Ngulube E, Ofori-Anyinam O, Vekemans J, Chimpeni P, Lievens M, Wilson TP, Njiramʼmadzi J, Mendoza YG, Leach A Abstract BACKGROUND: In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titres when co-administered with Expanded Programme on Immunisation (EPI) vaccines (0,1,2-month schedule) at 6-12 weeks compared to 5-17 months at first vaccination. Alternative infant immunisation schedules within the EPI were investigated. METHODS: This phase II, open, single site (Blantyre, Malawi) trial was conducted in infants aged 1-7 days. Subjects were equally randomised across seven groups to receive three doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14, 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received BCG+OPV at ≤7 days, DTPwHepB/Hib+OPV at 6,10,14 weeks and measles vaccine at 9 months; one RTS,S/AS01E group and the control additionally received hepatitis B vaccination at ≤7 days. Serum anti-CS antibody geometric mean concentration (GMC; ELISA) and safety were assessed up to age 18 months. RESULTS: Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS,S/AS01E vaccination compared to control was observed. Compared to the standard 6,10,14 week schedule, anti-CS antibody GMC ratios post-Dose 3 were significantly higher in the 10,14,26 week group only (ratio 1.80; 95%CI:1.24, 2.60); RTS,S/AS01E vaccination at ≤7 days, 10,14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95%CI:0.38, 0.92). CONCLUSIONS: Initiation of RTS,S/AS01E vaccination above six weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated, but produced a comparatively lower immune response. REGISTRATION: Clinical Trials.gov identifier: NCT01231503GlaxoSmithKline Study ID number: 111315 (Malaria-057). PMID: 29432383 [PubMed – as supplied by publisher]

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Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization…

Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide.

Posted by on 11 Feb 2018 | Tagged as: Hepatitis B Alternative Medicine

Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide. Sci Rep. 2018 Feb 09;8(1):2769 Authors: Kaneko M, Futamura Y, Tsukuda S, Kondoh Y, Sekine T, Hirano H, Fukano K, Ohashi H, Saso W, Morishita R, Matsunaga S, Kawai F, Ryo A, Park SY, Suzuki R, Aizaki H, Ohtani N, Sureau C, Wakita T, Osada H, Watashi K Abstract Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture. One of such compound, NPD8716, a coumarin derivative, interacted with NTCP and inhibited HBV infection without causing cytotoxicity. Consistent with its NTCP interaction capacity, this compound was shown to block viral attachment to host hepatocytes. NPD8716 also prevented the infection with hepatitis D virus, but not hepatitis C virus, in agreement with NPD8716 specifically inhibiting NTCP-mediated infection. Analysis of derivative compounds showed that the anti-HBV activity of compounds was apparently correlated with the affinity to NTCP and the capacity to impair NTCP-mediated bile acid uptake. These results are the first to show that the chemical array technology represents a powerful platform to identify novel viral entry inhibitors. PMID: 29426822 [PubMed – in process]

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Chemical array system, a platform to identify novel hepatitis B virus entry inhibitors targeting sodium taurocholate cotransporting polypeptide.