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[PMID]:28411240
[Au] Autor:Anasir MI; Caria S; Skinner MA; Kvansakul M
[Ad] Endereço:From the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia and.
[Ti] Título:Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039.
[So] Source:J Biol Chem;292(22):9010-9021, 2017 Jun 02.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies including the mimicry of prosurvival Bcl-2 proteins. One such viral prosurvival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis, we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering, and X-ray crystallography. Here, we report that the fowlpox virus prosurvival protein FPV039 promiscuously binds to cellular proapoptotic Bcl-2 and engages all major proapoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular proapoptotic Bcl-2 with affinities comparable with those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular prosurvival Bcl-2 proteins and closely mimics the structure of the prosurvival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan-Bcl-2 protein inhibitor that can engage all host BH3-only proteins, as well as Bcl-2-associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/química
Vírus da Varíola das Aves Domésticas/química
Proteínas Virais/química
[Mh] Termos MeSH secundário: Animais
Proteínas Reguladoras de Apoptose/genética
Proteínas Reguladoras de Apoptose/metabolismo
Proteínas Aviárias/química
Proteínas Aviárias/genética
Proteínas Aviárias/metabolismo
Galinhas
Cristalografia por Raios X
Vírus da Varíola das Aves Domésticas/genética
Vírus da Varíola das Aves Domésticas/metabolismo
Seres Humanos
Proteína de Sequência 1 de Leucemia de Células Mieloides/química
Proteína de Sequência 1 de Leucemia de Células Mieloides/genética
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo
Domínios Proteicos
Proteínas Virais/genética
Proteínas Virais/metabolismo
Proteína X Associada a bcl-2/química
Proteína X Associada a bcl-2/genética
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Avian Proteins); 0 (BAX protein, human); 0 (MCL1 protein, human); 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (Viral Proteins); 0 (bcl-2-Associated X Protein)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768879


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[PMID]:28056224
[Au] Autor:Townsend DG; Trivedi S; Jackson RJ; Ranasinghe C
[Ad] Endereço:Molecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia.
[Ti] Título:Recombinant fowlpox virus vector-based vaccines: expression kinetics, dissemination and safety profile following intranasal delivery.
[So] Source:J Gen Virol;98(3):496-505, 2017 Mar.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We have previously established that mucosal uptake of recombinant fowlpox virus (rFPV) vaccines is far superior to other vector-based vaccines. Specifically, intranasal priming with rFPV vaccines can recruit unique antigen-presenting cells, which induce excellent mucosal and systemic HIV-specific CD8+ T-cell immunity. In this study, we have for the first time investigated the in vivo dissemination, safety and expression kinetics of rFPV post intranasal delivery using recombinant viruses expressing green fluorescent protein or mCherry. Both confocal microscopy of tissue sections using green fluorescent protein and in vivo Imaging System (IVIS) spectrum live animal and whole organ imaging studies using mCherry revealed that (i) the peak antigen expression occurs 12 to 24 h post vaccination and no active viral gene expression is detected 96 h post vaccination. (ii) The virus only infects the initial vaccination site (lung and nasal cavity) and does not disseminate to distal sites such as the spleen or gut. (iii) More importantly, rFPV does not cross the olfactory receptor neuron pathway. Collectively, our findings indicate that rFPV vector-based vaccines have all the hallmarks of a safe and effective mucosal delivery vector, suitable for clinical evaluation.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/administração & dosagem
Vacinas contra a AIDS/efeitos adversos
Vírus da Varíola das Aves Domésticas
Antígenos HIV/administração & dosagem
Antígenos HIV/efeitos adversos
Vacinas Sintéticas/efeitos adversos
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/metabolismo
Administração Intranasal
Animais
Trato Gastrointestinal/metabolismo
Vetores Genéticos/administração & dosagem
Vetores Genéticos/efeitos adversos
Proteínas de Fluorescência Verde/análise
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Antígenos HIV/metabolismo
Proteínas Luminescentes/análise
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Pulmão/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Imagem Molecular
Mucosa Nasal/metabolismo
Baço/metabolismo
Vacinação
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/imunologia
Vacinas Sintéticas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (HIV Antigens); 0 (Luminescent Proteins); 0 (Vaccines, Synthetic); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000702


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[PMID]:27610735
[Au] Autor:Ogasawara F; Yamamoto Y; Sato Y; Fukunari K; Murata K; Yaegashi G; Goto M; Murakami R
[Ad] Endereço:A Iwate Central Livestock Hygiene Service Center, 390-5 Sunakomi, Takizawa, Iwate 020-0605, Japan.
[Ti] Título:Concurrent Fowlpox and Candidiasis Diseases in Backyard Chickens with Unusual Pox Lesions in the Bursa of Fabricius.
[So] Source:Avian Dis;60(3):705-8, 2016 Sep.
[Is] ISSN:1938-4351
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Concurrent fowlpox and candidiasis diseases occurred in a backyard chicken flock. Four deceased chickens (one Nagoya breed and three white silkie chickens) were examined for diagnosis. At necropsy, white curd-like plaques were observed in the crop. Fungal elements that stained positive for Candida albicans with immunohistochemistry were distributed throughout the tongue, choanal mucosa, esophagus, and crop. Typical fowlpox lesions, composed of proliferating epithelial cells with ballooning degeneration and viral intracytoplasmic inclusions, were observed in the conjunctiva, nasal mucosa, and skin around the cloaca. Interestingly, hyperplastic interfollicular epithelium with rare virus inclusions was observed in the bursa of Fabricius (BF). Some bursal follicles were replaced by proliferating epithelial cells. These proliferating cells immunohistochemically stained positive for cytokeratin. PCR and subsequent genetic sequencing detected the C. albicans gene in the crop, and fowlpox virus genes in the BF. These results indicate that this outbreak was a rare presentation of fowlpox in spontaneously infected chickens, with unusual pox lesions in the BF.
[Mh] Termos MeSH primário: Candidíase/veterinária
Galinhas
Coinfecção/veterinária
Surtos de Doenças/veterinária
Varíola Aviária/epidemiologia
Doenças das Aves Domésticas/epidemiologia
[Mh] Termos MeSH secundário: Animais
Candida/isolamento & purificação
Candidíase/diagnóstico
Candidíase/epidemiologia
Candidíase/microbiologia
Coinfecção/diagnóstico
Coinfecção/epidemiologia
Coinfecção/microbiologia
Varíola Aviária/diagnóstico
Varíola Aviária/virologia
Vírus da Varíola das Aves Domésticas/isolamento & purificação
Japão/epidemiologia
Masculino
Doenças das Aves Domésticas/diagnóstico
Doenças das Aves Domésticas/microbiologia
Doenças das Aves Domésticas/virologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160910
[St] Status:MEDLINE
[do] DOI:10.1637/11397-022416-Case.1


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[PMID]:26953946
[Au] Autor:Barreda CB
[Ad] Endereço:A Comisión de Investigaciones Científicas de la Provincia Buenos Aires, Argentina.
[Ti] Título:Relationship Between Values of Fowlpox ELISA and the Presence of "Takes" After Vaccination.
[So] Source:Avian Dis;60(1):67-9, 2016 Mar.
[Is] ISSN:1938-4351
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Values from an ELISA for evaluating the immune response induced by a commercial vaccine against fowlpox virus and the lesion at the site of inoculation (i.e., swelling of the skin or a pox where the vaccine was applied) were compared. The ELISA was carried out with an antigen prepared by precipitation of a cell culture-propagated virus suspension with ammonium sulfate and concentration by centrifugation. A 0.1 M acetate buffer (pH 5) was used as the sensitizing solution for maximum specific binding of the antigen to the microplate plastic well. Four experiments were conducted where the birds were bled once a week before and after vaccination and then were examined simultaneously for evidence of "takes." This study showed that there is a relationship between the ELISA values to the fowlpox vaccine that are considered positive and the presence of postvaccination lesions.
[Mh] Termos MeSH primário: Galinhas
Ensaio de Imunoadsorção Enzimática/veterinária
Vírus da Varíola das Aves Domésticas/imunologia
Varíola Aviária/imunologia
Imunidade Inata
Doenças das Aves Domésticas/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Varíola Aviária/virologia
Organismos Livres de Patógenos Específicos
Vacinação/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Vaccines)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160309
[St] Status:MEDLINE
[do] DOI:10.1637/11160-051615-ResNote.1


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[PMID]:25651753
[Au] Autor:Le Loc'h G; Paul MC; Camus-Bouclainville C; Bertagnoli S
[Ad] Endereço:RENECO Wildlife Consultants LLC, Abu Dhabi, UAE. g.leloch@hotmail.fr.
[Ti] Título:Outbreaks of Pox Disease Due to Canarypox-Like and Fowlpox-Like Viruses in Large-Scale Houbara Bustard Captive-Breeding Programmes, in Morocco and the United Arab Emirates.
[So] Source:Transbound Emerg Dis;63(6):e187-e196, 2016 Dec.
[Is] ISSN:1865-1682
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Infectious diseases can be serious threats for the success of reinforcement programmes of endangered species. Houbara Bustard species (Chlamydotis undulata and Chlamydotis macqueenii), whose populations declined in the last decades, have been captive-bred for conservation purposes for more than 15 years in North Africa and the Middle East. Field observations show that pox disease, caused by avipoxviruses (APV), regularly emerges in conservation projects of Houbara Bustard, despite a very strict implementation of both vaccination and biosecurity. Data collected from captive flocks of Houbara Bustard in Morocco from 2006 through 2013 and in the United Arab Emirates from 2011 through 2013 were analysed, and molecular investigations were carried out to define the virus strains involved. Pox cases (n = 2311) were observed during more than half of the year (88% of the months in Morocco, 54% in the United Arab Emirates). Monthly morbidity rates showed strong variations across the time periods considered, species and study sites: Four outbreaks were described during the study period on both sites. Molecular typing revealed that infections were mostly due to canarypox-like viruses in Morocco while fowlpox-like viruses were predominant in the United Arab Emirates. This study highlights that APV remain a major threat to consider in bird conservation initiatives.
[Mh] Termos MeSH primário: Vírus da Varíola dos Canários/isolamento & purificação
Surtos de Doenças/veterinária
Vírus da Varíola das Aves Domésticas/isolamento & purificação
Varíola Aviária/epidemiologia
Infecções por Poxviridae/veterinária
Vacinação/veterinária
[Mh] Termos MeSH secundário: Animais
Aves
Cruzamento
Vírus da Varíola dos Canários/genética
Conservação dos Recursos Naturais
Feminino
Varíola Aviária/mortalidade
Varíola Aviária/virologia
Vírus da Varíola das Aves Domésticas/genética
Masculino
Marrocos/epidemiologia
Infecções por Poxviridae/epidemiologia
Infecções por Poxviridae/mortalidade
Infecções por Poxviridae/virologia
Emirados Árabes Unidos/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150206
[St] Status:MEDLINE
[do] DOI:10.1111/tbed.12330


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[PMID]:25649538
[Au] Autor:Mizuguchi T; Torigoe T; Satomi F; Shima H; Kutomi G; Ota S; Ishii M; Hayashi H; Asakura S; Hirohashi Y; Meguro M; Kimura Y; Nishidate T; Okita K; Ishino M; Miyamoto A; Hatakenaka M; Sato N; Hirata K
[Ad] Endereço:Department of Surgery, Surgical Oncology, Sapporo Medical University, Sapporo, Hokkaido 060-8543, Japan. tmizu@sapmed.ac.jp.
[Ti] Título:Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?
[So] Source:Surg Today;46(2):139-48, 2016 Feb.
[Is] ISSN:1436-2813
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.
[Mh] Termos MeSH primário: Vacinas Anticâncer/uso terapêutico
Carcinoma Ductal Pancreático/terapia
Neoplasias Pancreáticas/terapia
[Mh] Termos MeSH secundário: Vacinas Bacterianas
Antígeno Carcinoembrionário
Ensaios Clínicos como Assunto
Vírus da Varíola das Aves Domésticas
Gastrinas
Genes ras/genética
Proteínas de Choque Térmico
Proteínas Inibidoras de Apoptose
Cinesina
Listeria monocytogenes
Mucina-1
Mutação
Peptídeos
Telomerase
Vacinas Atenuadas
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
Vacinas Virais
Proteínas WT1
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (BIRC5 protein, human); 0 (Bacterial Vaccines); 0 (Cancer Vaccines); 0 (Carcinoembryonic Antigen); 0 (GVAX vaccine); 0 (Gastrins); 0 (Heat-Shock Proteins); 0 (Inhibitor of Apoptosis Proteins); 0 (KIF20A protein, human); 0 (MUC1 protein, human); 0 (Mucin-1); 0 (Peptides); 0 (Vaccines, Attenuated); 0 (Viral Vaccines); 0 (WT1 Proteins); 0 (WT1 protein, human); 0 (gastrin immunogen); EC 2.7.10.1 (KDR protein, human); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2); EC 2.7.7.49 (TERT protein, human); EC 2.7.7.49 (Telomerase); EC 3.6.4.4 (Kinesin)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150205
[St] Status:MEDLINE
[do] DOI:10.1007/s00595-015-1120-8


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[PMID]:26473675
[Au] Autor:Roy B; Joardar SN; Samanta I; Das PK; Alam SS; Nandi S
[Ad] Endereço:A Department of Veterinary Microbiology and.
[Ti] Título:Detection of T- and B-cell Target Antigens of Fowlpox Virus Isolated from Backyard Chickens in India.
[So] Source:Avian Dis;59(2):249-54, 2015 Jun.
[Is] ISSN:0005-2086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With the aim of assessing the antigenic characteristics of a circulating pool of fowlpox virus (FPV) that exists in the backyard poultry system in India, one of the field isolates generated was characterized by in vitro immunologic techniques. FPV was isolated from clinically positive fowlpox cases (n  =  10) from the Jhargram (West Midnapur district) and Kakdwip (South 24 Pargana district) areas of West Bengal State, India. Initially, FPV-specific PCR was performed for confirmation of the samples. Isolation of FPV was done using embryonated chicken eggs and the choreoallantoic membrane route. Subsequently, FPV antigen was prepared from chicken embryo fibroblast cell culture-adapted field isolate. Biologic transmission of FPV was performed in Rhode Island red chickens experimentally to assess humoral and cell-mediated immune (CMI) responses. High level of anti-FPV antibodies were observed in test birds as assessed by indirect ELISA. Seroreactive polypeptides (B-cell antigens) of FPV antigen with molecular weights of 44.5, 66.5, 75, 90.5, and 99 kDa were detected by western blot analysis. Significant increases in CMI responses were observed in inoculated chickens as assessed by lymphocyte proliferation assay, cytotoxicity assay, and T-cell immunoblotting. The predominant T-cell antigen of FPV detected had a molecular weight of 66.5 kDa. The present study revealed the antigenic characteristics of FPV that exists in backyard poultry system in West Bengal for the first time, thus exploring the rationality of designing future T- and B-cell vaccines against fowlpox.
[Mh] Termos MeSH primário: Antígenos Virais/imunologia
Linfócitos B/fisiologia
Galinhas
Vírus da Varíola das Aves Domésticas/metabolismo
Varíola Aviária/imunologia
Linfócitos T/fisiologia
[Mh] Termos MeSH secundário: Animais
Antígenos Virais/metabolismo
Varíola Aviária/epidemiologia
Índia/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Viral)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:151019
[Lr] Data última revisão:
151019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151017
[St] Status:MEDLINE
[do] DOI:10.1637/11031-020415-Reg


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[PMID]:26048472
[Au] Autor:Li J; Yang T; Xu Q; Sun E; Feng Y; Lv S; Zhang Q; Wang H; Wu D
[Ad] Endereço:The Key Laboratory of Veterinary Public Health, Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
[Ti] Título:DNA vaccine prime and recombinant FPV vaccine boost: an important candidate immunization strategy to control bluetongue virus type 1.
[So] Source:Appl Microbiol Biotechnol;99(20):8643-52, 2015 Oct.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Bluetongue virus (BTV) is the causative agent of bluetongue (BT), an important sheep disease that caused great economic loss to the sheep industry. There are 26 BTV serotypes based on the outer protein VP2. However, the serotypes BTV-1 and BTV-16 are the two most prevalent serotypes in China. Vaccination is the most effective method of preventing viral infections. Therefore, the need for an effective vaccine against BTV is urgent. In this study, DNA vaccines and recombinant fowlpox virus (rFPV) vaccines expressing VP2 alone or VP2 in combination with VP5 or co-expressing the VP2 and VP5 proteins of BTV-1 were evaluated in both mice and sheep. Several strategies were tested in mice, including DNA vaccine prime and boost, rFPV vaccine prime and boost, and DNA vaccine prime and rFPV vaccine boost. We then determined the best vaccine strategy in sheep. Our results indicated that a strategy combining a DNA vaccine prime (co-expressing VP2 and VP5) followed by an rFPV vaccine boost (co-expressing VP2 and VP5) induced a high titer of neutralizing antibodies in sheep. Therefore, our data suggest that a DNA vaccine consisting of a pCAG-(VP2+VP5) prime and an rFPV-(VP2+VP5) boost is an important candidate for the design of a novel vaccine against BTV-1.
[Mh] Termos MeSH primário: Vírus Bluetongue/imunologia
Bluetongue/prevenção & controle
Esquemas de Imunização
Vacinas de DNA/administração & dosagem
Vacinas de DNA/imunologia
Vacinas Virais/administração & dosagem
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Bluetongue/imunologia
Vírus Bluetongue/genética
Portadores de Fármacos
Vírus da Varíola das Aves Domésticas/genética
Camundongos
Ovinos
Resultado do Tratamento
Vacinas de DNA/genética
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vacinas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Drug Carriers); 0 (Vaccines, DNA); 0 (Vaccines, Synthetic); 0 (Viral Vaccines)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150916
[Lr] Data última revisão:
150916
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150607
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-015-6697-8


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[PMID]:25660110
[Au] Autor:Bissa M; Zanotto C; Pacchioni S; Volonté L; Venuti A; Lembo D; De Giuli Morghen C; Radaelli A
[Ad] Endereço:Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. Electronic address: massimiliano.bissa@studenti.unimi.it.
[Ti] Título:The L1 protein of human papilloma virus 16 expressed by a fowlpox virus recombinant can assemble into virus-like particles in mammalian cell lines but elicits a non-neutralising humoral response.
[So] Source:Antiviral Res;116:67-75, 2015 Apr.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Human papilloma virus (HPV)-16 is the prevalent genotype associated with cervical tumours. Virus-like-particle (VLP)-based vaccines have proven to be effective in limiting new infections of high-risk HPVs, but their high cost has hampered their use, especially in the poor developing countries. Avipox-based recombinants are replication-restricted to avian species and represent efficient and safe vectors also for immunocompromised hosts, as they can elicit a complete immune response. A new fowlpox virus recombinant encoding HPV-L1 (FPL1) was engineered and evaluated side-by-side with a FP recombinant co-expressing L1 and green fluorescent protein (FPL1GFP) for correct expression of L1 in vitro in different cell lines, as confirmed by Western blotting, immunofluorescence, real-time PCR, and electron microscopy. Mice were also immunised to determine its immunogenicity. Here, we demonstrate that the FPL1 recombinant better expresses L1 in the absence of GFP, correctly assembles structured capsomers into VLPs, and elicits an immune response in a preclinical animal model. To our knowledge, this is the first report of HPV VLPs assembled in eukaryotic cells using an avipox recombinant.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/imunologia
Proteínas do Capsídeo/metabolismo
Vírus da Varíola das Aves Domésticas/genética
Papillomavirus Humano 16/genética
Papillomavirus Humano 16/imunologia
Proteínas Oncogênicas Virais/imunologia
Proteínas Oncogênicas Virais/metabolismo
Vacinas contra Papillomavirus/imunologia
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Proteínas do Capsídeo/genética
Linhagem Celular
Imunofluorescência
Vetores Genéticos
Proteínas de Fluorescência Verde/genética
Seres Humanos
Camundongos
Microscopia Eletrônica
Proteínas Oncogênicas Virais/genética
Vacinas contra Papillomavirus/genética
Reação em Cadeia da Polimerase em Tempo Real
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (Oncogene Proteins, Viral); 0 (Papillomavirus Vaccines); 0 (Vaccines, Virus-Like Particle); 147336-22-9 (Green Fluorescent Proteins); 6LTE2DNX63 (L1 protein, Human papillomavirus type 16)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150210
[St] Status:MEDLINE


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[PMID]:25533418
[Au] Autor:DiPaola RS; Chen YH; Bubley GJ; Stein MN; Hahn NM; Carducci MA; Lattime EC; Gulley JL; Arlen PM; Butterfield LH; Wilding G
[Ad] Endereço:Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: Robert.DiPaola@rutgers.edu.
[Ti] Título:A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.
[So] Source:Eur Urol;68(3):365-71, 2015 Sep.
[Is] ISSN:1873-7560
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. OBJECTIVE: To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. DESIGN, SETTING, AND PARTICIPANTS: Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. RESULTS AND LIMITATIONS: In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. CONCLUSIONS: A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this population. PATIENT SUMMARY: These data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease.
[Mh] Termos MeSH primário: Antagonistas de Androgênios/uso terapêutico
Vacinas Anticâncer/uso terapêutico
Calicreínas/imunologia
Antígeno Prostático Específico/imunologia
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Vacinas Anticâncer/imunologia
Terapia Combinada
Progressão da Doença
Vírus da Varíola das Aves Domésticas/imunologia
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico
Seres Humanos
Calicreínas/sangue
Masculino
Meia-Idade
Antígeno Prostático Específico/sangue
Prostatectomia
Vírus Vaccinia/imunologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Cancer Vaccines); 0 (PROSTVAC); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141224
[St] Status:MEDLINE



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