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  1 / 3097 MEDLINE  
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[PMID]:29020058
[Au] Autor:McCurley NP; Domi A; Basu R; Saunders KO; LaBranche CC; Montefiori DC; Haynes BF; Robinson HL
[Ad] Endereço:GeoVax Inc., Smyrna, GA, United States of America.
[Ti] Título:HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
[So] Source:PLoS One;12(10):e0177863, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Neutralizantes/imunologia
Antígenos CD4/metabolismo
Infecções por HIV/imunologia
Infecções por HIV/transmissão
[Mh] Termos MeSH secundário: Animais
Formação de Anticorpos/imunologia
Sítios de Ligação
Feminino
Células HEK293
Antígenos HIV/imunologia
Seres Humanos
Macaca mulatta
Vacinas de DNA/imunologia
Vírus Vaccinia/imunologia
Vírus Vaccinia/ultraestrutura
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (HIV Antigens); 0 (Vaccines, DNA); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177863


  2 / 3097 MEDLINE  
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[PMID]:28689085
[Au] Autor:Das S; Boliar S; Samal S; Ahmed S; Shrivastava T; Shukla BN; Goswami S; Bansal M; Chakrabarti BK
[Ad] Endereço:THSTI-IAVI HIV Vaccine Design Program, Translational Health Science and Technology Institute, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad 121001, Haryana, India.
[Ti] Título:Identification and characterization of a naturally occurring, efficiently cleaved, membrane-bound, clade A HIV-1 Env, suitable for immunogen design, with properties comparable to membrane-bound BG505.
[So] Source:Virology;510:22-28, 2017 Oct.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Efficient cleavage of HIV-1 Env gp160 into its constituent subunits correlates with selective binding to neutralizing antibodies and are the closest mimetic of native, functional Envs. This was first demonstrated with the clade B Env, JRFL. The correlation between efficient cleavage and selective binding to neutralizing antibodies is the guiding principle for immunogen design for HIV vaccine. We have recently reported that Envs 4-2.J41 (clade C) and JRCSF (clade B) are also efficiently cleaved and show similar properties. However, an efficiently cleaved, membrane-bound clade A Env suitable for genetic vaccination has not been directly demonstrated. Here we report that BG505 and a new clade A Env, QB726.70M.ENV.C4 (or A5) are efficiently cleaved on cell membrane. A5 shows desirable antigenic properties comparable with BG505 on cell surface. A5SOSIP in supernatant displays majority of bNAb binding epitopes. Thus, both BG505 and A5 Envs can be used in DNA prime-protein boost vaccination studies.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Anti-HIV/imunologia
Antígenos HIV/imunologia
Antígenos HIV/metabolismo
Proteólise
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Membrana Celular/metabolismo
Epitopos/imunologia
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (HIV Antibodies); 0 (HIV Antigens); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170710
[St] Status:MEDLINE


  3 / 3097 MEDLINE  
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[PMID]:28686629
[Au] Autor:Wang L; Zhou KH; Zhao HP; Wang JH; Zheng HC; Yu Y; Chen W
[Ad] Endereço:The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
[Ti] Título:The characteristics of screening and confirmatory test results for HIV in Xi'an, China.
[So] Source:PLoS One;12(7):e0180071, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an. METHODS: A 4th-generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB). The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates. RESULTS: In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai (9.88%), XinChuang (10.87%) and Livzon (8.93%), p<0.05. CONCLUSION: HIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.
[Mh] Termos MeSH primário: Diagnóstico Precoce
Infecções por HIV/diagnóstico
HIV-1/isolamento & purificação
HIV-2/isolamento & purificação
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
China
Testes Diagnósticos de Rotina
Feminino
Anticorpos Anti-HIV/imunologia
Antígenos HIV/imunologia
Antígenos HIV/isolamento & purificação
Infecções por HIV/imunologia
Infecções por HIV/virologia
HIV-1/imunologia
HIV-1/patogenicidade
HIV-2/imunologia
HIV-2/patogenicidade
Seres Humanos
Masculino
Programas de Rastreamento
Meia-Idade
Proteínas Virais/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Antibodies); 0 (HIV Antigens); 0 (Viral Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180071


  4 / 3097 MEDLINE  
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[PMID]:28666370
[Au] Autor:Delaugerre C; Antoni G; Mahjoub N; Pialoux G; Cua E; Pasquet A; Hall N; Tremblay C; Cotte L; Capitant C; Chaix ML; Meyer L; Molina JM; IPERGAY Study Group
[Ad] Endereço:Virologie.
[Ti] Título:Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs.
[So] Source:J Infect Dis;216(3):382-386, 2017 Aug 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.
[Mh] Termos MeSH primário: Infecções por HIV/diagnóstico
Infecções por HIV/prevenção & controle
Imunoensaio/métodos
Profilaxia Pré-Exposição
[Mh] Termos MeSH secundário: Anticorpos Anti-HIV/sangue
Antígenos HIV/sangue
HIV-1
Seres Humanos
Programas de Rastreamento/métodos
RNA Viral/sangue
Estudos Retrospectivos
Sensibilidade e Especificidade
Testes Sorológicos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Antibodies); 0 (HIV Antigens); 0 (RNA, Viral)
[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:170702
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix297


  5 / 3097 MEDLINE  
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[PMID]:28592537
[Au] Autor:Mazzuca P; Marsico S; Schulze K; Mitola S; Pils MC; Giagulli C; Guzman CA; Caruso A; Caccuri F
[Ad] Endereço:Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy.
[Ti] Título:Role of Autophagy in HIV-1 Matrix Protein p17-Driven Lymphangiogenesis.
[So] Source:J Virol;91(16), 2017 Aug 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIDS-related lymphomas (ARLs) are expected to increase in the future since combined antiretroviral therapy (cART) enhances the life expectancy of HIV-1-infected (HIV ) patients but does not affect the occurrence of ARLs to the same extent as that of other tumors. Lymphangiogenesis is essential in supporting growth and metastatic spreading of ARLs. HIV-1 does not infect the neoplastic B cells, but HIV-1 proteins have been hypothesized to play a key role in sustaining a prolymphangiogenic microenvironment in lymphoid organs. The HIV-1 matrix protein p17 is detected in blood and accumulates in the germinal centers of lymph nodes of HIV patients under successful cART. The viral protein displays potent lymphangiogenic activity and This is, at least in part, mediated by the secretion of the lymphangiogenic factor endothelin-1, suggesting that activation of a secretory pathway sustains the lymphangiogenic activity of p17. Here, we show that the p17 lymphangiogenic activity occurs on human lymph node-derived lymphatic endothelial cells (LN-LECs) under stress conditions only and relies entirely on activation of an autophagy-based pathway. In fact, induction of autophagy by p17 promotes lymphangiogenesis, whereas pharmacological and genetic inhibition of autophagy inhibits p17-triggered lymphangiogenesis. Similarly, the vasculogenic activity of p17 was totally inhibited in autophagy-incompetent mice. Our findings reveal a previously unrecognized role of autophagy in lymphangiogenesis and open the way to identify novel treatment strategies aimed at inhibiting aberrant tumor-driven lymphangiogenesis in HIV patients. AIDS-related lymphomas (ARLs) are the most common malignancies in HIV-1-infected (HIV ) patients after the introduction of combined antiretroviral therapy (cART). Lymphangiogenesis is of critical importance in sustaining growth and metastasis of ARLs. Indeed, enhanced lymphangiogenesis occurs in the lymph nodes of HIV patients under successful cART. The HIV-1 matrix protein p17 is detected in blood and accumulates in the lymph node germinal centers even in the absence of virus replication. Several findings suggest a key role for p17 as a microenvironmental factor capable of promoting lymphangiogenesis. Here, we show that p17 promotes lymphangiogenesis of human lymph node-derived lymphatic endothelial cells (LN-LECs). The lymphangiogenic activity of p17 is sustained by an autophagy-based pathway that enables LN-LECs to release prolymphangiogenic factors into the extracellular microenvironment. Our findings indicate that specific targeting of autophagy may provide an important new tool for treating ARLs.
[Mh] Termos MeSH primário: Autofagia
Células Endoteliais/efeitos dos fármacos
Antígenos HIV/metabolismo
Linfangiogênese
Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Seres Humanos
Camundongos Endogâmicos C57BL
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Antigens); 0 (gag Gene Products, Human Immunodeficiency Virus); 0 (p17 protein, Human Immunodeficiency Virus Type 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE


  6 / 3097 MEDLINE  
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[PMID]:28498985
[Au] Autor:Keating SM; Pilcher CD; Jain V; Lebedeva M; Hampton D; Abdel-Mohsen M; Deng X; Murphy G; Welte A; Facente SN; Hecht F; Deeks SG; Pillai SK; Busch MP
[Ad] Endereço:Blood Systems Research Institute.
[Ti] Título:HIV Antibody Level as a Marker of HIV Persistence and Low-Level Viral Replication.
[So] Source:J Infect Dis;216(1):72-81, 2017 Jul 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Human immunodeficiency virus (HIV) antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals receiving antiretroviral therapy (ART). Methods: HIV antibody responses were measured over time in the presence or absence of suppressive ART and were compared to the HIV reservoir size and expression of antiviral restriction factors. Results: Among untreated individuals, including both elite controllers (ie, persons with a viral load of ≤40 copies/mL) and noncontrollers, antibody parameters were stable over time and correlated with the individual viral load. Viral suppression with ART led to a progressive decline in antibody responses after treatment induction that persisted for 5-7 years. Higher levels of HIV antibodies during suppressive therapy were associated with later initiation of ART after infection, with higher DNA and cell-associated RNA levels, and with lower expression of multiple anti-HIV host restriction factors. Discussion: These findings suggest that declining antibody levels during ART reflect lower levels of antigen production and/or viral replication in the persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV antibody assays may be useful indirect markers that enable efficient monitoring of the viral reservoir and suppression during functional-cure interventions.
[Mh] Termos MeSH primário: Anticorpos Anti-HIV/sangue
Infecções por HIV/sangue
HIV-1/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Terapia Antirretroviral de Alta Atividade
Biomarcadores/sangue
Perfilação da Expressão Gênica
Antígenos HIV/sangue
Infecções por HIV/tratamento farmacológico
HIV-1/genética
Seres Humanos
Estudos Longitudinais
RNA Viral/isolamento & purificação
Manejo de Espécimes
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (HIV Antibodies); 0 (HIV Antigens); 0 (RNA, Viral)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix225


  7 / 3097 MEDLINE  
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[PMID]:28372798
[Au] Autor:Almeida CA; van Miert P; O'Driscoll K; Zoet YM; Chopra A; Watson M; de Santis D; Witt C; John M; Claas FHJ; D'Orsogna LJ
[Ad] Endereço:Department of Clinical Immunology, Fiona Stanley Hospital, Perth, Australia; Pathwest Laboratory Medicine, Perth, Australia; Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
[Ti] Título:Stimulation of HIV-specific T cell clonotypes using allogeneic HLA.
[So] Source:Cell Immunol;316:32-40, 2017 Jun.
[Is] ISSN:1090-2163
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We hypothesized that HIV-specific CD8 T cell clonotypes can be stimulated by allogeneic HLA molecules. Multiple HIV-specific CD8 T cell clones were derived from 12 individuals with chronic HIV infection, specific for 13 different HIV Gag antigens and restricted to 7 different HLA molecules. The generated T cell clones were assayed for alloreactivity against a panel of single HLA class I expressing cell lines (SALs). HIV-specific T cells recognising at least one allogeneic HLA molecule could be identified from 7 of 12 patients tested. Allorecognition was associated with IFNγ cytokine production, CD137 upregulation and cytotoxicity, suggesting high avidity allo-stimulation. Allo-HLA recognition by HIV-specific T cells was specific to the HIV target peptide/HLA restriction and TCR TRBV usage of the T cells. HIV-specific T cells do crossreact against allogeneic HLA molecules in an epitope and TRBV specific manner. Therefore allo-HLA stimulation could be exploited to induce or augment HIV-specific T cell responses.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Antígenos HIV/imunologia
Infecções por HIV/imunologia
Antígenos HLA-A/imunologia
Antígenos HLA-B/imunologia
[Mh] Termos MeSH secundário: Linfócitos T CD8-Positivos/patologia
Células Cultivadas
Células Clonais/imunologia
Estudos de Coortes
Reações Cruzadas
Infecções por HIV/patologia
Seres Humanos
Memória Imunológica
Receptores de Antígenos de Linfócitos T/imunologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (HIV Antigens); 0 (HLA-A Antigens); 0 (HLA-B Antigens); 0 (Receptors, Antigen, T-Cell); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  8 / 3097 MEDLINE  
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[PMID]:28348274
[Au] Autor:Billeskov R; Wang Y; Solaymani-Mohammadi S; Frey B; Kulkarni S; Andersen P; Agger EM; Sui Y; Berzofsky JA
[Ad] Endereço:Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; rob@ssi.dk berzofsj@mail.nih.gov.
[Ti] Título:Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy.
[So] Source:J Immunol;198(9):3494-3506, 2017 May 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Adjuvantes Imunológicos/administração & dosagem
Linfócitos T CD4-Positivos/imunologia
Antígenos HIV/imunologia
HIV/metabolismo
Lipossomos/administração & dosagem
Poli I-C/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD8-Positivos/imunologia
Células Cultivadas
Citocinas/metabolismo
HIV/imunologia
Seres Humanos
Lipossomos/química
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Monoglicerídeos/química
Compostos de Amônio Quaternário/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (HIV Antigens); 0 (Liposomes); 0 (Monoglycerides); 0 (Quaternary Ammonium Compounds); 0 (monomycoloyl glycerol); 251IW5I21C (dimethyldioctadecylammonium); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1600965


  9 / 3097 MEDLINE  
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[PMID]:28275193
[Au] Autor:Chuang GY; Geng H; Pancera M; Xu K; Cheng C; Acharya P; Chambers M; Druz A; Tsybovsky Y; Wanninger TG; Yang Y; Doria-Rose NA; Georgiev IS; Gorman J; Joyce MG; O'Dell S; Zhou T; McDermott AB; Mascola JR; Kwong PD
[Ad] Endereço:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
[Ti] Título:Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity.
[So] Source:J Virol;91(10), 2017 May 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The HIV-1 envelope (Env) trimer is a target for vaccine design as well as a conformational machine that facilitates virus entry by transitioning between prefusion-closed, CD4-bound, and coreceptor-bound conformations by transitioning into a postfusion state. Vaccine designers have sought to restrict the conformation of the HIV-1 Env trimer to its prefusion-closed state as this state is recognized by most broadly neutralizing, but not nonneutralizing, antibodies. We previously identified a disulfide bond, I201C-A433C (DS), which stabilizes Env in the vaccine-desired prefusion-closed state. When placed into the context of BG505 SOSIP.664, a soluble Env trimer mimic developed by Sanders, Moore, and colleagues, the engineered DS-SOSIP trimer showed reduced conformational triggering by CD4. Here, we further stabilize DS-SOSIP through a combination of structure-based design and 96-well-based expression and antigenic assessment. From 103 designs, we identified one, named DS-SOSIP.4mut, with four additional mutations at the interface of potentially mobile domains of the prefusion-closed structure. We also determined the crystal structures of DS-SOSIP.4mut at 4.1-Å resolution and of an additional DS-SOSIP.6mut variant at 4.3-Å resolution, and these confirmed the formation of engineered disulfide bonds. Notably, DS-SOSIP.4mut elicited a higher ratio of tier 2 autologous titers versus tier 1 V3-sensitive titers than BG505 SOSIP.664. DS-SOSIP.4mut also showed reduced recognition of CD4 and increased thermostability. The improved antigenicity, thermostability, and immunogenicity of DS-SOSIP.4mut suggest utility as an immunogen or a serologic probe; moreover, the specific four alterations identified here, M154, M300, M302, and L320 (4mut), can also be transferred to other HIV-1 Env trimers of interest to improve their properties. One approach to elicit broadly neutralizing antibodies against HIV-1 is to stabilize the structurally flexible HIV-1 envelope (Env) trimer in a conformation that displays predominantly broadly neutralizing epitopes and few to no nonneutralizing epitopes. The prefusion-closed conformation of HIV-1 Env has been identified as one such preferred conformation, and a current leading vaccine candidate is the BG505 DS-SOSIP variant, comprising two disulfides and an Ile-to-Pro mutation of Env from strain BG505. Here, we introduced additional mutations to further stabilize BG505 DS-SOSIP in the vaccine-preferred prefusion-closed conformation. In guinea pigs, our best mutant, DS-SOSIP.4mut, elicited a significantly higher ratio of autologous versus V3-directed neutralizing antibody responses than the SOSIP-stabilized form. We also observed an improvement in thermostability and a reduction in CD4 affinity. With improved antigenicity, stability, and immunogenicity, DS-SOSIP.4mut-stabilized trimers may have utility as HIV-1 immunogens or in other antigen-specific contexts, such as with B-cell probes.
[Mh] Termos MeSH primário: Antígenos CD4/imunologia
Antígenos CD4/metabolismo
Antígenos HIV/imunologia
HIV-1/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/química
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/química
Vacinas contra a AIDS/imunologia
Animais
Anticorpos Neutralizantes/sangue
Anticorpos Neutralizantes/imunologia
Cobaias
Anticorpos Anti-HIV/sangue
Anticorpos Anti-HIV/imunologia
Antígenos HIV/química
Antígenos HIV/metabolismo
HIV-1/genética
Seres Humanos
Multimerização Proteica
Estabilidade Proteica
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (HIV Antibodies); 0 (HIV Antigens); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE


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[PMID]:28179536
[Au] Autor:García-Arriaza J; Perdiguero B; Heeney JL; Seaman MS; Montefiori DC; Yates NL; Tomaras GD; Ferrari G; Foulds KE; Roederer M; Self SG; Borate B; Gottardo R; Phogat S; Tartaglia J; Barnett SW; Burke B; Cristillo AD; Weiss DE; Lee C; Kibler KV; Jacobs BL; Wagner R; Ding S; Pantaleo G; Esteban M
[Ad] Endereço:Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
[Ti] Título:HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.
[So] Source:J Virol;91(9), 2017 May 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4 and CD8 T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the and vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene , an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4 and CD8 T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4 and CD8 T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions. It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection. Here we developed novel replicating poxvirus NYVAC-based HIV/AIDS vaccine candidates expressing clade C HIV-1 antigens, with one of them lacking the vaccinia virus B19 protein, an inhibitor of the type I interferon response. Immunization of nonhuman primates with these novel NYVAC-C-KC vectors and the protein component gp120 elicited high levels of T cell and humoral immune responses, with the vector containing a deletion in inducing a trend toward a higher magnitude of CD4 and CD8 T cell responses and neutralization of some HIV-1 strains. These poxvirus vectors could be considered HIV/AIDS vaccine candidates based on their activation of potential immune correlates of protection.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Neutralizantes/sangue
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Anticorpos Anti-HIV/sangue
Proteína gp120 do Envelope de HIV/imunologia
Vacinas de Partículas Semelhantes a Vírus/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/genética
Animais
Anticorpos Neutralizantes/imunologia
Citotoxicidade Celular Dependente de Anticorpos/imunologia
Anticorpos Anti-HIV/imunologia
Antígenos HIV/imunologia
Infecções por HIV/prevenção & controle
Interferon Tipo I/genética
Macaca mulatta
Masculino
Receptores de Interferon/genética
Receptores de Interferon/imunologia
Vacinação
Vírus Vaccinia/genética
Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Antigens); 0 (HIV Envelope Protein gp120); 0 (Interferon Type I); 0 (NYVAC-C vaccine); 0 (Receptors, Interferon); 0 (Vaccines, Virus-Like Particle); 0 (env Gene Products, Human Immunodeficiency Virus); 0 (gp140 envelope protein, Human immunodeficiency virus 1)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE



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