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[PMID]:27772623
[Au] Autor:Gajurel K; Stapleton JT
[Ad] Endereço:Department of Internal Medicine, University of Iowa, Iowa City, IA.
[Ti] Título:Hepatitis Viruses in Kidney Transplantation.
[So] Source:Semin Nephrol;36(5):386-396, 2016 09.
[Is] ISSN:1558-4488
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis viruses are named for their primary clinical illness, inflammation of the liver. Currently, six types of viruses are designated hepatitis viruses (A, B, C, D, E, and G), although only five of these cause hepatitis. Hepatitis viruses are composed of RNA and DNA viruses from different families and with different virologic properties, some of which typically cause acute hepatitis while others cause acute and chronic hepatitis. In addition to their role in liver disease, members of this group of viruses may cause a variety of pathologic changes in the kidney and other organs, and chronic infection may lead to cirrhosis in addition to raising a variety of important issues in the management of kidney transplant recipients. In this brief report, we review the virologic and clinical properties of each of the hepatitis viruses, and highlight the role of each virus in renal disease and kidney transplantation.
[Mh] Termos MeSH primário: Rejeição de Enxerto/prevenção & controle
Hepatite Viral Humana/induzido quimicamente
Imunossupressores/efeitos adversos
Falência Renal Crônica/cirurgia
Transplante de Rim
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Hepatite Viral Humana/diagnóstico
Hepatite Viral Humana/tratamento farmacológico
Hepatite Viral Humana/prevenção & controle
Seres Humanos
Vacinas contra Hepatite Viral/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Immunosuppressive Agents); 0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28914042
[Ti] Título:Meeting of the International Task Force for Disease Eradication, June 2017.
[Ti] Título:Réunion du Groupe spécial international pour l'éradication des maladies, juin 2017..
[So] Source:Wkly Epidemiol Rec;92(37):537-56, 2017 09 15.
[Is] ISSN:0049-8114
[Cp] País de publicação:Switzerland
[La] Idioma:eng; fre
[Mh] Termos MeSH primário: Comitês Consultivos
Erradicação de Doenças
Saúde Global
Hepatite B Crônica/prevenção & controle
Hepatite C Crônica/prevenção & controle
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Infecções Assintomáticas/epidemiologia
Fortalecimento Institucional
Comunicação
Erradicação de Doenças/organização & administração
Apoio Financeiro
Georgia
Saúde Global/estatística & dados numéricos
Metas
Vacinas contra Hepatite B/administração & dosagem
Hepatite B Crônica/tratamento farmacológico
Hepatite B Crônica/epidemiologia
Hepatite C Crônica/tratamento farmacológico
Hepatite C Crônica/epidemiologia
Seres Humanos
Recém-Nascido
Vigilância da População/métodos
Desenvolvimento de Programas
Vacinas contra Hepatite Viral/administração & dosagem
Organização Mundial da Saúde
[Pt] Tipo de publicação:CONGRESSES
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Hepatitis B Vaccines); 0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE


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[PMID]:28794021
[Au] Autor:Pierce BG; Boucher EN; Piepenbrink KH; Ejemel M; Rapp CA; Thomas WD; Sundberg EJ; Weng Z; Wang Y
[Ad] Endereço:Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA pierce@umd.edu yang.wang@umassmed.edu.
[Ti] Título:Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines. Hepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that is the target of broadly neutralizing antibodies. results in mice indicated that these antigens elicited epitope-specific neutralizing antibodies, with various degrees of potency and breadth. These promising results suggest that a rational design approach can be used to generate an effective vaccine for this virus.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/biossíntese
Anticorpos Antivirais/biossíntese
Epitopos/imunologia
Hepacivirus/imunologia
Vacinas contra Hepatite Viral/química
Vacinas contra Hepatite Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/imunologia
Desenho de Drogas
Epitopos/química
Camundongos
Proteínas do Envelope Viral/imunologia
Vacinas contra Hepatite Viral/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Epitopes); 0 (Viral Envelope Proteins); 0 (Viral Hepatitis Vaccines); 157184-61-7 (glycoprotein E2, Hepatitis C virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE


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[PMID]:28483064
[Au] Autor:Casillas SM; Bednarczyk RA
[Ad] Endereço:Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.
[Ti] Título:Missed Opportunities for Hepatitis A Vaccination, National Immunization Survey-Child, 2013.
[So] Source:J Pediatr;187:265-271.e1, 2017 Aug.
[Is] ISSN:1097-6833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To quantify the number of missed opportunities for vaccination with hepatitis A vaccine in children and assess the association of missed opportunities for hepatitis A vaccination with covariates of interest. STUDY DESIGN: Weighted data from the 2013 National Immunization Survey of US children aged 19-35 months were used. Analysis was restricted to children with provider-verified vaccination history (n = 13 460). Missed opportunities for vaccination were quantified by determining the number of medical visits a child made when another vaccine was administered during eligibility for hepatitis A vaccine, but hepatitis A vaccine was not administered. Cross-sectional bivariate and multivariate polytomous logistic regression were used to assess the association of missed opportunities for vaccination with child and maternal demographic, socioeconomic, and geographic covariates. RESULTS: In 2013, 85% of children in our study population had initiated the hepatitis A vaccine series, and 60% received 2 or more doses. Children who received zero doses of hepatitis A vaccine had an average of 1.77 missed opportunities for vaccination compared with 0.43 missed opportunities for vaccination in those receiving 2 doses. Children with 2 or more missed opportunities for vaccination initiated the vaccine series 6 months later than children without missed opportunities. In the fully adjusted multivariate model, children who were younger, had ever received WIC benefits, or lived in a state with childcare entry mandates were at a reduced odds for 2 or more missed opportunities for vaccination; children living in the Northeast census region were at an increased odds. CONCLUSIONS: Missed opportunities for vaccination likely contribute to the poor coverage for hepatitis A vaccination in children; it is important to understand why children are not receiving the vaccine when eligible.
[Mh] Termos MeSH primário: Hepatite A/prevenção & controle
Programas de Imunização/estatística & dados numéricos
Vacinas contra Hepatite Viral/administração & dosagem
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Estudos Transversais
Feminino
Seres Humanos
Lactente
Masculino
Inquéritos e Questionários
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


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[PMID]:28398489
[Au] Autor:Li D; Wang X; von Schaewen M; Tao W; Zhang Y; Heller B; Hrebikova G; Deng Q; Sun Q; Ploss A; Zhong J; Huang Z
[Ad] Endereço:Unit of Vaccinology and Antiviral Strategies.
[Ti] Título:Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates.
[So] Source:J Infect Dis;215(12):1824-1831, 2017 Jun 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: The global control of hepatitis C virus (HCV) infection remains a great burden, owing to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs), as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported that a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice. Here the sE2 vaccine was evaluated in non-human primates. Methods: Rhesus macaques were immunized with sE2 vaccine in combination with different adjuvants. Vaccine-induced NAbs in antisera were tested for neutralization activities against a panel of cell culture-derived HCV (HCVcc), while T-cell responses were evaluated in splenocytes, peripheral blood mononuclear cells, and hepatic lymphocytes. Results: sE2 is able to elicit NAbs against HCVcc harboring structural proteins from multiple HCV genotypes in rhesus macaques. Moreover, sE2-immunized macaques developed systemic and intrahepatic memory T cells specific for E2. A significant correlation between the sE2-specific immunoglobulin G titers and neutralization spectrum was observed, highlighting the essential role of sE2 immunogenicity on achieving broad NAbs. Conclusions: sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Hepacivirus/imunologia
Anticorpos Anti-Hepatite C/sangue
Linfócitos T/imunologia
Vacinas contra Hepatite Viral/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/uso terapêutico
Animais
Ensaio de Imunoadsorção Enzimática
Feminino
Genótipo
Hepacivirus/genética
Hepatite C/prevenção & controle
Hepatite C/virologia
Seres Humanos
Imunização
Leucócitos Mononucleares/imunologia
Fígado/imunologia
Fígado/virologia
Macaca mulatta
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Neutralizing); 0 (Hepatitis C Antibodies); 0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix180


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[PMID]:28374641
[Au] Autor:Hayes CN; Chayama K
[Ad] Endereço:a Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences , Hiroshima University , Hiroshima , Japan.
[Ti] Título:Why highly effective drugs are not enough: the need for an affordable solution to eliminating HCV.
[So] Source:Expert Rev Clin Pharmacol;10(6):583-594, 2017 Jun.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Because of the rapid pace of development of new direct-acting antiviral (DAA) drugs, chronic hepatitis C virus (HCV) infection is now increasingly considered curable. However, the emphasis on DAA therapies disregards key issues related to cost, availability, and antiviral resistance. Areas covered: This perspective provides an overview of current HCV therapies and the development of DAAs, followed by a discussion of the limitations of DAA therapy. A literature search was used to select relevant studies, and a web search for relevant news articles and press releases was conducted. Expert commentary: Despite cure rates exceeding 90%, now is not the time to declare victory against HCV but to reinforce recent progress by addressing the issues of cost and availability as well as by developing strategies to manage antiviral resistance. Future drug development efforts should place greater emphasis on targeting host factors required for HCV replication, for which the barrier to resistance is higher, and effort should continue to develop a vaccine against HCV. Finally, efforts should be made to facilitate large-scale screening in endemic areas to identify and treat patients as early as possible to reduce long-term risks of advanced liver disease and their attendant costs of management.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Desenho de Drogas
Hepatite C Crônica/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antivirais/economia
Antivirais/farmacologia
Custos de Medicamentos
Farmacorresistência Viral
Hepatite C Crônica/virologia
Seres Humanos
Vacinas contra Hepatite Viral/administração & dosagem
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2017.1313111


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[PMID]:28285495
[Au] Autor:Kalafateli M; Buzzetti E; Thorburn D; Davidson BR; Tsochatzis E; Gurusamy KS
[Ad] Endereço:Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK.
[Ti] Título:Pharmacological interventions for acute hepatitis C infection: an attempted network meta-analysis.
[So] Source:Cochrane Database Syst Rev;3:CD011644, 2017 03 13.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis, and instead, we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months.There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I = 0%). The proportion of people with any adverse events was higher with interferon-alpha and interferon-beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health-related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon-alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons.Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that interferon-alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health-related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct-acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct-acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high-quality randomised clinical trials are required.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Hepatite C/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença Aguda
Antivirais/efeitos adversos
Quimioterapia Combinada/efeitos adversos
Hepatite C Crônica/tratamento farmacológico
Seres Humanos
Interferon-alfa/efeitos adversos
Interferon-alfa/uso terapêutico
Metanálise em Rede
Polietilenoglicóis/efeitos adversos
Polietilenoglicóis/uso terapêutico
Qualidade de Vida
Ensaios Clínicos Controlados Aleatórios como Assunto
Proteínas Recombinantes/efeitos adversos
Proteínas Recombinantes/uso terapêutico
Ribavirina/efeitos adversos
Ribavirina/uso terapêutico
Vacinas contra Hepatite Viral/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Interferon-alpha); 0 (Recombinant Proteins); 0 (Viral Hepatitis Vaccines); 0 (hepatitis vaccine MTH 68-B); 30IQX730WE (Polyethylene Glycols); 49717AWG6K (Ribavirin); Q46947FE7K (peginterferon alfa-2a)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170313
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD011644.pub2


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[PMID]:28231679
[Au] Autor:Chen ZM; Ji SB; Shi XL; Zhao YY; Zhang XF; Jin H
[Ad] Endereço:School of Public Health, Southeast University, Nanjing 210009, China.
[Ti] Título:[Use the Markov-decision tree model to optimize vaccination strategies of hepatitis E among women aged 15 to 49].
[So] Source:Zhonghua Liu Xing Bing Xue Za Zhi;38(2):267-271, 2017 Feb 10.
[Is] ISSN:0254-6450
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49. The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies. Parameters of the models were estimated on the basis of published studies and experience of experts. Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model. Compared with non-vaccination group, strategy on post-screening vaccination with rate as 100%, could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives. After implementation of screening program and with the vaccination rate reaching 100%, the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 Yuan/QALY, respectively. Vaccination post to the implementation of a screening program, the result showed better benefit than the vaccination rate of 100%. Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects. If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23, the vaccination rate of 100% strategy was better than the post-screening vaccination strategy, otherwise the post-screening vaccination strategy appeared the optimal strategy. Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.
[Mh] Termos MeSH primário: Árvores de Decisões
Hepatite E/economia
Cadeias de Markov
Vacinação/estatística & dados numéricos
Vacinas contra Hepatite Viral/economia
[Mh] Termos MeSH secundário: Adolescente
Adulto
China/epidemiologia
Análise Custo-Benefício
Custos e Análise de Custo
Feminino
Hepatite E/epidemiologia
Hepatite E/prevenção & controle
Seres Humanos
Meia-Idade
Modelos Teóricos
Anos de Vida Ajustados por Qualidade de Vida
Vacinação/economia
Vacinas contra Hepatite Viral/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Hepatitis Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170224
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0254-6450.2017.02.026


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[PMID]:27997681
[Au] Autor:Vietheer PT; Boo I; Gu J; McCaffrey K; Edwards S; Owczarek C; Hardy MP; Fabri L; Center RJ; Poumbourios P; Drummer HE
[Ad] Endereço:Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
[Ti] Título:The core domain of hepatitis C virus glycoprotein E2 generates potent cross-neutralizing antibodies in guinea pigs.
[So] Source:Hepatology;65(4):1117-1131, 2017 Apr.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, vaccine development has been confounded because of HCV's high degree of antigenic variability and the preferential induction of type-specific immune responses with limited potency against heterologous viral strains and genotypes. We showed previously that deletion of the three variable regions from the E2 receptor-binding domain (Δ123) increases the ability of human broadly neutralizing antibodies (bNAbs) to inhibit E2-CD81 receptor interactions, suggesting improved bNAb epitope exposure. In this study, the immunogenicity of Δ123 was examined. We show that high-molecular-weight forms of Δ123 elicit distinct antibody specificities with potent and broad neutralizing activity against all seven HCV genotypes. Antibody competition studies revealed that immune sera raised to high-molecular-weight Δ123 was poly specific, given that it inhibited the binding of human bNAbs directed to three major neutralization epitopes on E2. By contrast, the immune sera raised to monomeric Δ123 predominantly blocked the binding of a non-neutralizing antibody to Δ123, while having reduced ability to block bNAb binding to E2, and neutralization was largely toward the homologous genotype. This increased ability of oligomeric Δ123 to generate bNAbs correlates with occlusion of the non-neutralizing face of E2 in this glycoprotein form. CONCLUSION: The results from this study reveal new information on the antigenic and immunogenic potential of E2-based immunogens and provide a pathway for the development of a simple, recombinant protein-based prophylactic vaccine for HCV with potential for universal protection. (Hepatology 2017;65:1117-1131).
[Mh] Termos MeSH primário: Hepacivirus/genética
Hepatite C/genética
Proteínas do Envelope Viral/genética
Vacinas contra Hepatite Viral/farmacologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/imunologia
Especificidade de Anticorpos/genética
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Epitopos/genética
Genótipo
Cobaias
Hepacivirus/imunologia
Hepatite C/imunologia
Anticorpos Anti-Hepatite C/imunologia
Distribuição Aleatória
Estatísticas não Paramétricas
Proteínas do Envelope Viral/imunologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (Hepatitis C Antibodies); 0 (Viral Envelope Proteins); 0 (Viral Hepatitis Vaccines); 157184-61-7 (glycoprotein E2, Hepatitis C virus)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28989


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[PMID]:27795422
[Au] Autor:Logan M; Law J; Wong JA; Hockman D; Landi A; Chen C; Crawford K; Kundu J; Baldwin L; Johnson J; Dahiya A; LaChance G; Marcotrigiano J; Law M; Foung S; Tyrrell L; Houghton M
[Ad] Endereço:Li Ka Shing Institute of Virology, Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, Canada logan@ualberta.ca michael.houghton@ualberta.ca.
[Ti] Título:Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.
[So] Source:J Virol;91(1), 2017 Jan 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A recombinant strain HCV1 (hepatitis C virus [HCV] genotype 1a) gpE1/gpE2 (E1E2) vaccine candidate was previously shown by our group to protect chimpanzees and generate broad cross-neutralizing antibodies in animals and humans. In addition, recent independent studies have highlighted the importance of conserved neutralizing epitopes in HCV vaccine development that map to antigenic clusters in E2 or the E1E2 heterodimer. E1E2 can be purified using Galanthis nivalis lectin agarose (GNA), but this technique is suboptimal for global production. Our goal was to investigate a high-affinity and scalable method for isolating E1E2. We generated an Fc tag-derived (Fc-d) E1E2 that was selectively captured by protein G Sepharose, with the tag being removed subsequently using PreScission protease. Surprisingly, despite the presence of the large Fc tag, Fc-d E1E2 formed heterodimers similar to those formed by GNA-purified wild-type (WT) E1E2 and exhibited nearly identical binding profiles to HCV monoclonal antibodies that target conserved neutralizing epitopes in E2 (HC33.4, HC84.26, and AR3B) and the E1E2 heterodimer (AR4A and AR5A). Antisera from immunized mice showed that Fc-d E1E2 elicited anti-E2 antibody titers and neutralization of HCV pseudotype viruses similar to those with WT E1E2. Competition enzyme-linked immunosorbent assays (ELISAs) showed that antisera from immunized mice inhibited monoclonal antibody binding to neutralizing epitopes. Antisera from Fc-d E1E2-immunized mice exhibited stronger competition for AR3B and AR5A than the WT, whereas the levels of competition for HC84.26 and AR4A were similar. We anticipate that Fc-d E1E2 will provide a scalable purification and manufacturing process using protein A/G-based chromatography. IMPORTANCE: A prophylactic HCV vaccine is still needed to control this global disease despite the availability of direct-acting antivirals. Previously, we demonstrated that a recombinant envelope glycoprotein (E1E2) vaccine (genotype 1a) elicited cross-neutralizing antibodies from human volunteers. A challenge for isolating the E1E2 antigen is the reliance on GNA, which is unsuitable for large scale-up and global vaccine delivery. We have generated a novel Fc domain-tagged E1E2 antigen that forms functional heterodimers similar to those with native E1E2. Affinity purification and removal of the Fc tag from E1E2 resulted in an antigen with a nearly identical profile of cross-neutralizing epitopes. This antigen elicited anti-HCV antibodies that targeted conserved neutralizing epitopes of E1E2. Owing to the high selectivity and cost-effective binding capacity of affinity resins for capture of the Fc-tagged rE1E2, we anticipate that our method will provide a means for large-scale production of this HCV vaccine candidate.
[Mh] Termos MeSH primário: Hepacivirus/imunologia
Anticorpos Anti-Hepatite C/biossíntese
Hepatite C/prevenção & controle
Proteínas Recombinantes de Fusão/biossíntese
Proteínas do Envelope Viral/biossíntese
Vacinas contra Hepatite Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/biossíntese
Anticorpos Monoclonais/química
Anticorpos Neutralizantes/biossíntese
Anticorpos Neutralizantes/química
Antígenos Virais/química
Antígenos Virais/imunologia
Proteínas de Bactérias/química
Proteínas de Bactérias/isolamento & purificação
Cromatografia em Agarose/métodos
Reações Cruzadas
Epitopos/química
Epitopos/imunologia
Hepacivirus/química
Hepatite C/imunologia
Hepatite C/virologia
Anticorpos Anti-Hepatite C/química
Seres Humanos
Soros Imunes/química
Fragmentos Fc das Imunoglobulinas/biossíntese
Fragmentos Fc das Imunoglobulinas/genética
Fragmentos Fc das Imunoglobulinas/isolamento & purificação
Camundongos
Testes de Neutralização
Dobramento de Proteína
Multimerização Proteica
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/isolamento & purificação
Vacinação
Vacinas Sintéticas
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/isolamento & purificação
Vacinas contra Hepatite Viral/administração & dosagem
Vacinas contra Hepatite Viral/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Neutralizing); 0 (Antigens, Viral); 0 (Bacterial Proteins); 0 (E1 protein, Hepatitis C virus); 0 (Epitopes); 0 (Hepatitis C Antibodies); 0 (IgG Fc-binding protein, Streptococcus); 0 (Immune Sera); 0 (Immunoglobulin Fc Fragments); 0 (Recombinant Fusion Proteins); 0 (Vaccines, Synthetic); 0 (Viral Envelope Proteins); 0 (Viral Hepatitis Vaccines); 157184-61-7 (glycoprotein E2, Hepatitis C virus)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE



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