Base de dados : MEDLINE
Pesquisa : B04.280.030.500.700 [Categoria DeCS]
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  1 / 281 MEDLINE  
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[PMID]:28460470
[Au] Autor:Cheng T; Song Y; Zhang Y; Zhang C; Yin J; Chi Y; Zhou D
[Ad] Endereço:Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai 200031, China.
[Ti] Título:A novel oncolytic adenovirus based on simian adenovirus serotype 24.
[So] Source:Oncotarget;8(16):26871-26885, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-ΔE3 for cancer treatment. AdC7-SP/E1A-ΔE3 was constructed by replacing the E1A promoter with tumor specific promoter survivin promoter and deleting E3 region using direct cloning methods based on simian adenovirus serotype 24 (namely AdC7). We showed that AdC7-SP/E1A-ΔE3 significantly killed tumor cell lines NCI-H508 and Huh7, and inhibited tumor growth in both NCI-H508 and Huh7 xenograft tumor models. Importantly, AdC7-SP/E1A-ΔE3 exhibited the antitumor efficacy via systemic administration. Mechanistically, infected cells were killed by AdC7-SP/E1A-ΔE3 via the p53-independent mitochondrial apoptosis pathway in which phosphorylation of BAD markedly declined and the expresses of Bik significantly went up. Therefore, AdC7-SP/E1A-ΔE3 is a promising candidate for liver and colon tumor treatment.
[Mh] Termos MeSH primário: Adenovirus dos Símios/classificação
Adenovirus dos Símios/genética
Vetores Genéticos/genética
Vírus Oncolíticos/genética
[Mh] Termos MeSH secundário: Proteínas E1A de Adenovirus/genética
Animais
Apoptose/genética
Linhagem Celular Tumoral
Efeito Citopatogênico Viral
Modelos Animais de Doenças
Deleção de Genes
Expressão Gênica
Engenharia Genética
Terapia Genética
Vetores Genéticos/administração & dosagem
Vetores Genéticos/efeitos adversos
Seres Humanos
Proteínas Inibidoras de Apoptose/genética
Camundongos
Mitocôndrias/genética
Terapia Viral Oncolítica
Especificidade de Órgãos/genética
Regiões Promotoras Genéticas
Sorogrupo
Transdução de Sinais
Carga Tumoral
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
Replicação Viral
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus E1A Proteins); 0 (BIRC5 protein, human); 0 (Inhibitor of Apoptosis Proteins); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15845


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[PMID]:28792942
[Au] Autor:Capucci S; Wee EG; Schiffner T; LaBranche CC; Borthwick N; Cupo A; Dodd J; Dean H; Sattentau Q; Montefiori D; Klasse PJ; Sanders RW; Moore JP; Hanke T
[Ad] Endereço:The Jenner Institute, University of Oxford, Oxford, United Kingdom.
[Ti] Título:HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers.
[So] Source:PLoS One;12(8):e0181886, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1.BG505s (C) and MVA.BG505s (M) vaccine-infected cells, respectively, were cleaved and in a native-like conformation. Rabbits were immunized intramuscularly with these vaccine vectors and in some cases boosted with ISCOMATRIX™-adjuvanted BG505s protein trimer (P), using CCC, MMM, PPP, CPP, MPP and CMP vaccine regimens. We found that the peak trimer-binding antibody and tier-1A and autologous tier-2 nAb responses induced by the CC, CM, PPP, CPP, MPP and CMP regimens were comparable, although only PPP induced autologous tier-2 nAbs in all the immunized animals. Three animals developed weak heterologous tier-2 nAbs. These results demonstrate that ChAdOx1 and MVA vectors are useful delivery modalities for not only T-cell, but also antibody vaccine development.
[Mh] Termos MeSH primário: Adenovirus dos Símios/imunologia
Anticorpos Neutralizantes/imunologia
Anticorpos Anti-HIV/imunologia
HIV-1/imunologia
Vírus Vaccinia/imunologia
Vacinas Virais/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/imunologia
Animais
Linhagem Celular
Células HEK293
Seres Humanos
Multimerização Proteica/imunologia
Coelhos
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (MVA vaccine); 0 (Viral Vaccines); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181886


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[PMID]:28750871
[Au] Autor:Parker IK; Price KA; Singletary T; Srinivasan P; Smith JM; Curtis KA
[Ad] Endereço:Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
[Ti] Título:A multiplex assay for detection of SHIV plasma and mucosal IgG and IgA.
[So] Source:J Immunol Methods;450:34-40, 2017 Nov.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Evaluating antibody maturation provides valuable data to characterize immune responses to HIV infection and can provide insight into biomedical intervention efficacy. It is important to develop assays that evaluate antibody maturation in both plasma and mucosal compartments. The nonhuman primate model provides a controlled system to collect temporal data that are integral to assessing intervention strategies. We report the development of a novel multiplex assay, based on the Bio-Plex platform, to evaluate plasma and mucosal IgG and IgA avidity and maturation against simian/human immunodeficiency virus (SHIV) in this controlled system. Vaginal mucosa and plasma samples were collected from a prior study evaluating the efficacy of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR) against SHIVSF162P3 challenge in female pigtailed macaques. For validation of the multiplex assay, specimens from six SHIV-infected placebo animals and one TDF breakthrough animal were evaluated. For SHIV and HIV envelope analytes, antibody levels and avidity in both compartments continued to mature post-infection. Maturation of IgG and IgA levels was similar in each compartment, however, mucosal antibody levels tended to be more variable. This SHIV assay elucidates IgG/IgA antibody kinetics in the plasma and vaginal mucosa and will be a valuable tool in vaccine and other biomedical intervention studies in the nonhuman primate model.
[Mh] Termos MeSH primário: Adenovirus dos Símios/imunologia
Anticorpos Anti-HIV/sangue
Imunoensaio/métodos
Imunoglobulina A/sangue
Imunoglobulina G/sangue
Membrana Mucosa/imunologia
Testes Sorológicos/métodos
Síndrome de Imunodeficiência Adquirida dos Símios/diagnóstico
Vagina/imunologia
[Mh] Termos MeSH secundário: Adenina/administração & dosagem
Adenina/análogos & derivados
Adenovirus dos Símios/efeitos dos fármacos
Administração Intravaginal
Animais
Fármacos Anti-HIV/administração & dosagem
Biomarcadores/sangue
Modelos Animais de Doenças
Feminino
Interações Hospedeiro-Patógeno
Imunidade Humoral
Imunidade nas Mucosas
Macaca nemestrina
Membrana Mucosa/virologia
Ácidos Fosforosos/administração & dosagem
Valor Preditivo dos Testes
Reprodutibilidade dos Testes
Soroconversão
Síndrome de Imunodeficiência Adquirida dos Símios/sangue
Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Fatores de Tempo
Vagina/virologia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine); 0 (Anti-HIV Agents); 0 (Biomarkers); 0 (HIV Antibodies); 0 (Immunoglobulin A); 0 (Immunoglobulin G); 0 (Phosphorous Acids); JAC85A2161 (Adenine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE


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[PMID]:28719652
[Au] Autor:Moyo N; Borthwick NJ; Wee EG; Capucci S; Crook A; Dorrell L; Hanke T
[Ad] Endereço:The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens.
[So] Source:PLoS One;12(7):e0181382, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition. Here, we assessed the durability of these responses. METHODS: Vaccine recipients in trial HIV-CORE 002 were invited to provide a blood sample at 1 and 2 years after vaccination. Their PBMCs were tested in IFN-γ ELISPOT, 25-analyte Luminex, CFSE proliferation and intracellular cytokine staining assays, the last enhanced by HLA-peptide dextramer analysis. RESULTS: 12/12 (1 year) and 8/8 (2 years) returning subjects had median (range) of 990 (150-2495) and 763 (70-1745) IFN-γ SFU/106 PBMC specific for HIVconsv, respectively, and recognized 5 (1-6) out of 6 peptide pools at 2 years. Over one-half of the HIVconsv-specific cells expressed at least 3 functions IFN-γ, TNF-α and CD107a, and were capable of proliferation. Among dextramer-reactive cells, naïve, transitional, effector and terminally differentiated memory subsets were similarly represented. CONCLUSIONS: First generation HIVconsv vaccine induced human T cells, which were plurifunctional and persisted for at least 2 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01151319.
[Mh] Termos MeSH primário: Adenovirus dos Símios/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Sequência Conservada
HIV-1/imunologia
Vacinas de DNA/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Seguimentos
Antígenos HLA/metabolismo
Seres Humanos
Especificidade da Espécie
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens); 0 (MVA vaccine); 0 (Vaccines, DNA); 0 (Viral Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181382


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[PMID]:28498840
[Au] Autor:Osman M; Mistry A; Keding A; Gabe R; Cook E; Forrester S; Wiggins R; Di Marco S; Colloca S; Siani L; Cortese R; Smith DF; Aebischer T; Kaye PM; Lacey CJ
[Ad] Endereço:Centre for Immunology and Infection, Dept. of Biology and Hull York Medical School, University of York, Heslington, York, United Kingdom.
[Ti] Título:A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.
[So] Source:PLoS Negl Trop Dis;11(5):e0005527, 2017 May.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359).
[Mh] Termos MeSH primário: Vacinas contra Leishmaniose/imunologia
Vacinas contra Leishmaniose/isolamento & purificação
Leishmaniose Cutânea/prevenção & controle
Leishmaniose Cutânea/terapia
Leishmaniose Visceral/prevenção & controle
Leishmaniose Visceral/terapia
[Mh] Termos MeSH secundário: Adenovirus dos Símios/genética
Adolescente
Adulto
Antígenos de Protozoários/genética
Antígenos de Protozoários/imunologia
Linfócitos T CD8-Positivos/imunologia
Portadores de Fármacos
ELISPOT
Feminino
Citometria de Fluxo
Voluntários Saudáveis
Seres Humanos
Injeções Intramusculares
Interferon gama/secreção
Leishmania/genética
Leishmania/imunologia
Vacinas contra Leishmaniose/administração & dosagem
Vacinas contra Leishmaniose/efeitos adversos
Masculino
Meia-Idade
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/efeitos adversos
Vacinas Sintéticas/imunologia
Vacinas Sintéticas/isolamento & purificação
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Drug Carriers); 0 (Leishmaniasis Vaccines); 0 (Vaccines, Synthetic); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005527


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[PMID]:27894993
[Au] Autor:Dadáková E; Chrudimský T; Brozová K; Modrý D; Celer V; Hrazdilová K
[Ad] Endereço:Department of Infectious Diseases and Microbiology, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic.
[Ti] Título:New adenoviruses from new primate hosts - growing diversity reveals taxonomic weak points.
[So] Source:Mol Phylogenet Evol;107:305-307, 2017 Feb.
[Is] ISSN:1095-9513
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The knowledge of the closest human relatives of human adenoviruses (AdVs) such as adenoviruses found in nonhuman primates is still limited, despite the growing importance of adenoviruses in vaccine development, gene and cancer therapy. We examined 153 stool samples of 17 non-human primate species and detected adenoviral DNA sequences of DNA polymerase (DPOL) gene in 54 samples (35%), originating from 12 out of 17 primate species. We further sequenced 15 hexon gene fragments and based on the phylogenetic analysis we propose two new provisional species SAdV-H and SAdV-I. Our study shows extensive diversity of adenoviral strains forming separate clades often from closely related host species from old world monkeys suggesting the existence of new species of AdVs and shows the necessity for clear ICTV guidelines for final establishment of so far provisional AdV species.
[Mh] Termos MeSH primário: Adenovirus dos Símios/classificação
Adenovirus dos Símios/genética
Variação Genética
Interações Hospedeiro-Patógeno
Primatas/virologia
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Teorema de Bayes
Seres Humanos
Nucleotídeos/genética
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nucleotides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161130
[St] Status:MEDLINE


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[PMID]:25426834
[Au] Autor:Ledgerwood JE; DeZure AD; Stanley DA; Coates EE; Novik L; Enama ME; Berkowitz NM; Hu Z; Joshi G; Ploquin A; Sitar S; Gordon IJ; Plummer SA; Holman LA; Hendel CS; Yamshchikov G; Roman F; Nicosia A; Colloca S; Cortese R; Bailer RT; Schwartz RM; Roederer M; Mascola JR; Koup RA; Sullivan NJ; Graham BS; VRC 207 Study Team
[Ad] Endereço:From the Vaccine Research Center (J.E.L., A.D.D., D.A.S., E.E.C., L.N., M.E.E., N.M.B., A.P., S.S., I.J.G., S.A.P., L.A.H., C.S.H., G.Y., R.T.B., R.M.S., M.R., J.R.M., R.A.K., N.J.S., B.S.G.) and the Biostatistics Research Branch, Division of Clinical Research (Z.H., G.J.), National Institute of All
[Ti] Título:Chimpanzee Adenovirus Vector Ebola Vaccine.
[So] Source:N Engl J Med;376(10):928-938, 2017 03 09.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. METHODS: We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10 particle units or 2×10 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 8 weeks after vaccination; in addition, longer-term vaccine durability was assessed at 48 weeks after vaccination. RESULTS: In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10 particle-unit dose than in the group that received the 2×10 particle-unit dose (geometric mean titer against the Zaire antigen at week 4, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2×10 particle-unit dose than among those who received the 2×10 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07) at week 4. Assessment of the durability of the antibody response showed that titers remained high at week 48, with the highest titers in those who received the 2×10 particle-unit dose. CONCLUSIONS: Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×10 particle-unit dose, glycoprotein Zaire-specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates, and responses were sustained to week 48. Phase 2 studies and efficacy trials assessing cAd3-EBO are in progress. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866 .).
[Mh] Termos MeSH primário: Vacinas contra Ebola/imunologia
Ebolavirus/imunologia
Doença pelo Vírus Ebola/prevenção & controle
[Mh] Termos MeSH secundário: Adenovirus dos Símios
Adulto
Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Vacinas contra Ebola/administração & dosagem
Vacinas contra Ebola/efeitos adversos
Febre/etiologia
Vetores Genéticos
Glicoproteínas/imunologia
Seres Humanos
Masculino
Meia-Idade
Pan troglodytes
Linfócitos T/fisiologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Ebola Vaccines); 0 (Glycoproteins)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:141127
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1410863


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[PMID]:27978537
[Au] Autor:Mensah VA; Gueye A; Ndiaye M; Edwards NJ; Wright D; Anagnostou NA; Syll M; Ndaw A; Abiola A; Bliss C; Gomis JF; Petersen I; Ogwang C; Dieye T; Viebig NK; Lawrie AM; Roberts R; Nicosia A; Faye B; Gaye O; Leroy O; Imoukhuede EB; Ewer KJ; Bejon P; Hill AV; Cisse B; MVVC group
[Ad] Endereço:Parasitology department, Faculty of Medicine University Cheikh Anta Diop, Dakar, Senegal.
[Ti] Título:Safety, Immunogenicity and Efficacy of Prime-Boost Vaccination with ChAd63 and MVA Encoding ME-TRAP against Plasmodium falciparum Infection in Adults in Senegal.
[So] Source:PLoS One;11(12):e0167951, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. More recently, a study in Kenyan adults, similar to that reported here, showed substantial efficacy against P. falciparum infection. One hundred and twenty healthy male volunteers, living in a malaria endemic area of Senegal were randomised to receive either the Chimpanzee adenovirus (ChAd63) ME-TRAP as prime vaccination, followed eight weeks later by modified vaccinia Ankara (MVA) also encoding ME-TRAP as booster, or two doses of anti-rabies vaccine as a comparator. Prior to follow-up, antimalarials were administered to clear parasitaemia and then participants were monitored by PCR for malaria infection for eight weeks. The primary endpoint was time-to-infection with P. falciparum malaria, determined by two consecutive positive PCR results. Secondary endpoints included adverse event reporting, measures of cellular and humoral immunogenicity and a meta-analysis of combined vaccine efficacy with the parallel study in Kenyan adults.We show that this pre-erythrocytic malaria vaccine is safe and induces significant immunogenicity, with a peak T-cell response at seven days after boosting of 932 Spot Forming Cells (SFC)/106 Peripheral Blood Mononuclear Cells(PBMC) compared to 57 SFC/ 106 PBMCs in the control group. However, a vaccine efficacy was not observed: 12 of 57 ME-TRAP vaccinees became PCR positive during the intensive monitoring period as compared to 13 of the 58 controls (P = 0.80). This trial confirms that vaccine efficacy against malaria infection in adults may be rapidly assessed using this efficient and cost-effective clinical trial design. Further efficacy evaluation of this vectored candidate vaccine approach in other malaria transmission settings and age-de-escalation into the main target age groups for a malaria vaccine is in progress.
[Mh] Termos MeSH primário: Vacinas Antimaláricas/imunologia
Vacinas Antimaláricas/uso terapêutico
Malária Falciparum/imunologia
Malária Falciparum/prevenção & controle
Plasmodium falciparum/patogenicidade
Proteínas de Protozoários/imunologia
[Mh] Termos MeSH secundário: Adenovirus dos Símios/genética
Adulto
Antimaláricos/uso terapêutico
Seres Humanos
Vacinas Antimaláricas/efeitos adversos
Malária Falciparum/genética
Masculino
Plasmodium falciparum/genética
Plasmodium falciparum/imunologia
Reação em Cadeia da Polimerase
Proteínas de Protozoários/genética
Senegal
Vacinação/efeitos adversos
Vacinação/métodos
Vírus Vaccinia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antimalarials); 0 (Malaria Vaccines); 0 (Protozoan Proteins); 120300-02-9 (thrombospondin-related adhesive protein, protozoan)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0167951


  9 / 281 MEDLINE  
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[PMID]:27109630
[Au] Autor:Afolabi MO; Tiono AB; Adetifa UJ; Yaro JB; Drammeh A; Nébié I; Bliss C; Hodgson SH; Anagnostou NA; Sanou GS; Jagne YJ; Ouedraogo O; Tamara C; Ouedraogo N; Ouedraogo M; Njie-Jobe J; Diarra A; Duncan CJ; Cortese R; Nicosia A; Roberts R; Viebig NK; Leroy O; Lawrie AM; Flanagan KL; Kampman B; Bejon P; Imoukhuede EB; Ewer KJ; Hill AV; Bojang K; Sirima SB
[Ad] Endereço:Medical Research Council Unit, Fajara, The Gambia.
[Ti] Título:Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.
[So] Source:Mol Ther;24(8):1470-7, 2016 Aug.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity.
[Mh] Termos MeSH primário: Adenovirus dos Símios
Epitopos
Vetores Genéticos
Vacinas Antimaláricas/imunologia
Malária/prevenção & controle
Vírus Vaccinia
[Mh] Termos MeSH secundário: África Ocidental/epidemiologia
Animais
Anticorpos Antiprotozoários/sangue
Anticorpos Antiprotozoários/imunologia
Criança
Pré-Escolar
ELISPOT
Epitopos/imunologia
Gâmbia
Vetores Genéticos/efeitos adversos
Seres Humanos
Imunização Secundária
Lactente
Recém-Nascido
Malária/epidemiologia
Vacinas Antimaláricas/administração & dosagem
Vacinas Antimaláricas/efeitos adversos
Avaliação de Resultados (Cuidados de Saúde)
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Epitopes); 0 (Malaria Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160426
[St] Status:MEDLINE
[do] DOI:10.1038/mt.2016.83


  10 / 281 MEDLINE  
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[PMID]:27052571
[Au] Autor:Cappuccini F; Stribbling S; Pollock E; Hill AV; Redchenko I
[Ad] Endereço:The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
[Ti] Título:Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer.
[So] Source:Cancer Immunol Immunother;65(6):701-13, 2016 06.
[Is] ISSN:1432-0851
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime-boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEAP1), induced strong sustained antigen-specific CD8+ T-cell responses in C57BL/6 and BALB/c male mice. Unexpectedly, the high vaccine immunogenicity translated into relatively low protective efficacy in the murine transplantable and spontaneous models of prostate cancer. A combination of the vaccine with PD-1 blocking antibody significantly improved survival of the animals, with 80 % of mice remaining tumour-free. These results indicate that the ChAdOx1-MVA vaccination regime targeting STEAP1 combined with PD-1 therapy might have high therapeutic potential in the clinic.
[Mh] Termos MeSH primário: Adenovirus dos Símios/genética
Anticorpos Monoclonais/farmacologia
Vacinas Anticâncer/genética
Vacinas Anticâncer/imunologia
Vetores Genéticos/genética
Neoplasias da Próstata/genética
Neoplasias da Próstata/imunologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa
Animais
Apresentação do Antígeno/imunologia
Antígenos de Neoplasias/imunologia
Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Terapia Combinada
Modelos Animais de Doenças
Seres Humanos
Imunização
Imunização Secundária
Imunomodulação
Imunoterapia
Interferon gama/metabolismo
Masculino
Camundongos
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Neoplasias da Próstata/patologia
Neoplasias da Próstata/terapia
Subpopulações de Linfócitos T/imunologia
Subpopulações de Linfócitos T/metabolismo
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antigens, Neoplasm); 0 (Antineoplastic Agents); 0 (Cancer Vaccines); 0 (Programmed Cell Death 1 Receptor); 0 (Steap protein, mouse); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160408
[St] Status:MEDLINE
[do] DOI:10.1007/s00262-016-1831-8



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