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[PMID]:28461133
[Au] Autor:Chen DJ; Yao JD
[Ad] Endereço:Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. Electronic address: dchen@uwhealth.org.
[Ti] Título:Comparison of turnaround time and total cost of HIV testing before and after implementation of the 2014 CDC/APHL Laboratory Testing Algorithm for diagnosis of HIV infection.
[So] Source:J Clin Virol;91:69-72, 2017 06.
[Is] ISSN:1873-5967
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Updated recommendations for HIV diagnostic laboratory testing published by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories incorporate 4th generation HIV immunoassays, which are capable of identifying HIV infection prior to seroconversion. OBJECTIVES: The purpose of this study was to compare turnaround time and cost between 3rd and 4th generation HIV immunoassay-based testing algorithms for initially reactive results. STUDY DESIGN: The clinical microbiology laboratory database at Mayo Clinic, Rochester, MN was queried for 3rd generation (from November 2012 to May 2014) and 4th generation (from May 2014 to November 2015) HIV immunoassay results. All results from downstream supplemental testing were recorded. Turnaround time (defined as the time of initial sample receipt in the laboratory to the time the final supplemental test in the algorithm was resulted) and cost (based on 2016 Medicare reimbursement rates) were assessed. RESULTS: A total of 76,454 and 78,998 initial tests were performed during the study period using the 3rd generation and 4th generation HIV immunoassays, respectively. There were 516 (0.7%) and 581 (0.7%) total initially reactive results, respectively. Of these, 304 (58.9%) and 457 (78.7%) were positive by supplemental testing. There were 10 (0.01%) cases of acute HIV infection identified with the 4th generation algorithm. The most frequent tests performed to confirm an HIV-positive case using the 3rd generation algorithm, which were reactive initial immunoassay and positive HIV-1 Western blot, took a median time of 1.1 days to complete at a cost of $45.00. In contrast, the most frequent tests performed to confirm an HIV-positive case using the 4th generation algorithm, which included a reactive initial immunoassay and positive HIV-1/-2 antibody differentiation immunoassay for HIV-1, took a median time of 0.4 days and cost $63.25. Overall median turnaround time was 2.2 and 1.5 days, and overall median cost was $63.90 and $72.50 for 3rd and 4th generation algorithms, respectively. CONCLUSIONS: Both 3rd and 4th generation HIV immunoassays had similar total numbers of tests performed and positivity rates during the study period. A greater proportion of reactive 4th generation immunoassays were confirmed to be positive, and the 4th generation algorithm identified several cases of acute HIV infection that would have been missed by the 3rd generation algorithm. The 4th generation algorithm had a more rapid turnaround time but higher cost for confirmed positive HIV infections and overall, compared to the 3rd generation algorithm.
[Mh] Termos MeSH primário: Sorodiagnóstico da AIDS
Algoritmos
Infecções por HIV/diagnóstico
Imunoensaio
[Mh] Termos MeSH secundário: Sorodiagnóstico da AIDS/economia
Centers for Disease Control and Prevention (U.S.)
Custos e Análise de Custo
Anticorpos Anti-HIV/sangue
Infecções por HIV/economia
Infecções por HIV/virologia
HIV-1/genética
HIV-1/imunologia
HIV-2/genética
HIV-2/imunologia
Seres Humanos
Imunoensaio/economia
Imunoensaio/métodos
Programas de Rastreamento/economia
Programas de Rastreamento/legislação & jurisprudência
Programas de Rastreamento/métodos
Técnicas de Amplificação de Ácido Nucleico/economia
Técnicas de Amplificação de Ácido Nucleico/métodos
Sensibilidade e Especificidade
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIV Antibodies)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 10410 MEDLINE  
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[PMID]:28461065
[Au] Autor:Hu D; Bowder D; Wei W; Thompson J; Wilson MA; Xiang SH
[Ad] Endereço:Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
[Ti] Título:Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design.
[So] Source:Vaccine;35(23):3067-3075, 2017 05 25.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Anti-HIV/imunologia
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/imunologia
Imunogenicidade da Vacina
Triptofano/química
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/administração & dosagem
Vacinas contra a AIDS/química
Substituição de Aminoácidos
Animais
Anticorpos Neutralizantes/imunologia
Antígenos CD4
Desenho de Drogas
Epitopos/química
Cobaias
Anticorpos Anti-HIV/sangue
HIV-1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (Epitopes); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp120); 8DUH1N11BX (Tryptophan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  3 / 10410 MEDLINE  
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[PMID]:27771962
[Au] Autor:Fink E; Fuller K; Agan B; Berger EA; Saphire A; Quinnan GV; Elder JH
[Ad] Endereço:1 Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, California.
[Ti] Título:Humoral Antibody Responses to HIV Viral Proteins and to CD4 Among HIV Controllers, Rapid and Typical Progressors in an HIV-Positive Patient Cohort.
[So] Source:AIDS Res Hum Retroviruses;32(12):1187-1197, 2016 12.
[Is] ISSN:1931-8405
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC. All of the HIV patient samples were positive for antibodies to HIV gp120 and p24 and 80% showed evidence of hypergammaglobulinemia. Approximately 10% of cohort members were positive for antibodies to CD4, but we noted no significant correlation relevant to DP. There were statistically significant differences between the groups concerning the level of humoral response to gp120 and Gag. However, we observed no distinction in ability of anti-gp120 antibodies purified from each group to neutralize infection. In addition, there was a statistically significant difference in ADCC, with elite controllers exhibiting significantly lower levels of ADCC than the other five groups. We detected IgA anti-gp120 antibodies, but did not correlate their presence with either DP or ADCC levels. The results are consistent with the interpretation that the humoral antibody response to the antigens assessed here represents a signature of the level of viremia but does not correlate with clinical status of HIV infection.
[Mh] Termos MeSH primário: Formação de Anticorpos
Autoanticorpos/sangue
Antígenos CD4/imunologia
Progressão da Doença
Anticorpos Anti-HIV/sangue
Infecções por HIV/imunologia
Proteínas do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Autoanticorpos/imunologia
Ensaio de Imunoadsorção Enzimática
Feminino
Anticorpos Anti-HIV/imunologia
Infecções por HIV/patologia
Seres Humanos
Masculino
Estudos Prospectivos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Autoantibodies); 0 (CD4 Antigens); 0 (HIV Antibodies); 0 (Human Immunodeficiency Virus Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  4 / 10410 MEDLINE  
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[PMID]:29051051
[Au] Autor:Sun Z; Yan L; Tang J; Qian Q; Lenberg J; Zhu D; Liu W; Wu K; Wang Y; Lu S
[Ad] Endereço:Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, United States. Electronic address: sunz@njhealth.org.
[Ti] Título:Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies.
[So] Source:Virus Res;243:75-82, 2018 01 02.
[Is] ISSN:1872-7492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization. The isolation and characterization of large panels of potent human broadly neutralizing antibodies has revealed new insights into the principles of antibody-mediated neutralization of HIV. In this paper, we review the current effective techniques in broadly neutralizing antibody isolation.
[Mh] Termos MeSH primário: Anticorpos Anti-HIV/isolamento & purificação
Infecções por HIV/imunologia
HIV-1/imunologia
Técnicas Imunológicas
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/imunologia
Anticorpos Neutralizantes/isolamento & purificação
Anticorpos Anti-HIV/imunologia
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Técnicas Imunológicas/métodos
Técnicas Imunológicas/tendências
Testes de Neutralização
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (HIV Antibodies)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE


  5 / 10410 MEDLINE  
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[PMID]:28463876
[Au] Autor:Anderson DJ; Politch JA; Zeitlin L; Hiatt A; Kadasia K; Mayer KH; Ruprecht RM; Villinger F; Whaley KJ
[Ad] Endereço:aDepartments of Obstetrics and Gynecology Boston University School of Medicine, Boston, Massachusetts bMapp Biopharmaceutical, San Diego California cDepartment of Molecular Medicine, Boston University School of Medicine dFenway Health, Harvard Medical School, Boston, Massachusetts eTexas Biomedical Institute, Southwest National Primate Research Center, San Antonio, Texas fNew Iberia Primate Center, New Iberia, Louisiana, USA.
[Ti] Título:Systemic and topical use of monoclonal antibodies to prevent the sexual transmission of HIV.
[So] Source:AIDS;31(11):1505-1517, 2017 Jul 17.
[Is] ISSN:1473-5571
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:: Passive immunization, the transfer of antibodies to a nonimmune individual to provide immunological protection, has been used for over 100 years to prevent and treat human infectious diseases. The introduction of techniques to produce human mAbs has revolutionized the field, and a large number of human mAbs have been licensed for the treatment of cancer, autoimmune and inflammatory diseases. With the recent discovery and production of highly potent broadly neutralizing and other multifunctional antibodies to HIV, mAbs are now being considered for HIV therapy and prophylaxis. In this review, we briefly present recent advances in the anti-HIV mAb field and outline strategies for the selection, engineering and production of human mAbs, including the modification of their structure for optimized stability and function. We also describe results from nonhuman primate studies and phase 1 clinical trials that have tested the safety, tolerability, pharmacokinetics, and efficacy of mAb-based HIV prevention strategies, and discuss the future of parenteral and topical mAb administration for the prevention of HIV transmission.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Anticorpos Monoclonais/farmacologia
Anticorpos Anti-HIV/efeitos dos fármacos
Anticorpos Anti-HIV/imunologia
Infecções por HIV/prevenção & controle
Imunização Passiva
Profilaxia Pré-Exposição/métodos
Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
[Mh] Termos MeSH secundário: Administração Tópica
Animais
Anticorpos Monoclonais/administração & dosagem
Feminino
Infecções por HIV/transmissão
HIV-1/efeitos dos fármacos
Seres Humanos
Imunização Passiva/métodos
Reto/virologia
Síndrome de Imunodeficiência Adquirida dos Símios/transmissão
Vírus da Imunodeficiência Símia/efeitos dos fármacos
Resultado do Tratamento
Vagina/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (HIV Antibodies)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1097/QAD.0000000000001521


  6 / 10410 MEDLINE  
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[PMID]:28458036
[Au] Autor:Meador LR; Kessans SA; Kilbourne J; Kibler KV; Pantaleo G; Roderiguez ME; Blattman JN; Jacobs BL; Mor TS
[Ad] Endereço:Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ, USA; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
[Ti] Título:A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
[So] Source:Virology;507:242-256, 2017 07.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/administração & dosagem
Proteína gp41 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Imunização/métodos
Tabaco/metabolismo
Vírus Vaccinia/fisiologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/imunologia
Animais
Anticorpos Neutralizantes/imunologia
Formação de Anticorpos
Feminino
Vetores Genéticos/genética
Vetores Genéticos/fisiologia
Anticorpos Anti-HIV/imunologia
Proteína gp41 do Envelope de HIV/administração & dosagem
Proteína gp41 do Envelope de HIV/genética
Infecções por HIV/prevenção & controle
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Imunização Secundária
Camundongos
Camundongos Endogâmicos C57BL
Tabaco/genética
Tabaco/virologia
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vírus Vaccinia/genética
Replicação Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/administração & dosagem
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp41); 0 (Vaccines, Virus-Like Particle); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  7 / 10410 MEDLINE  
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[PMID]:28747500
[Au] Autor:Hraber P; Rademeyer C; Williamson C; Seaman MS; Gottardo R; Tang H; Greene K; Gao H; LaBranche C; Mascola JR; Morris L; Montefiori DC; Korber B
[Ad] Endereço:Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA pth@lanl.gov btk@lanl.gov.
[Ti] Título:Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envs either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do not know what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products. HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half of current HIV-1 infections, and is a focus for vaccine design and testing. Standard reference reagents, particularly virus panels to study neutralization by antibodies, are crucial for developing cost-effective and yet rigorous and reproducible assays against diverse examples of this variable virus. We developed clade C-specific panels for use as standardized reagents to monitor complex polyclonal sera for neutralization activity and to characterize the potency and breadth of cross-reactive neutralization by monoclonal antibodies, whether engineered or isolated from infected individuals. We chose from 200 southern African, clade C envelope-pseudotyped viruses with neutralization titers against 16 broadly neutralizing antibodies and 30 sera from chronic clade C infections. We selected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sensitivities. Use of standard virus panels can facilitate comparison of results across studies and sites.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Anticorpos Neutralizantes/imunologia
Anticorpos Anti-HIV/imunologia
HIV-1/imunologia
Testes de Neutralização/métodos
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Infecções por HIV/imunologia
Infecções por HIV/prevenção & controle
Infecções por HIV/terapia
HIV-1/classificação
HIV-1/genética
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171215
[Lr] Data última revisão:
171215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE


  8 / 10410 MEDLINE  
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[PMID]:29065142
[Au] Autor:C Guardo A; Gómez CE; Díaz-Brito V; Pich J; Arnaiz JA; Perdiguero B; García-Arriaza J; González N; Sorzano COS; Jiménez L; Jiménez JL; Muñoz-Fernández MÁ; Gatell JM; Alcamí J; Esteban M; López Bernaldo de Quirós JC; García F; Plana M; RISVAC02boost study
[Ad] Endereço:Immunopathology and Cellular Immunology, AIDS Research Group, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
[Ti] Título:Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization.
[So] Source:PLoS One;12(10):e0186602, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. RESULTS: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. CONCLUSIONS: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923610.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
HIV-1/imunologia
Imunização Secundária
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/efeitos adversos
Anticorpos Neutralizantes/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Ensaio de Imunoadsorção Enzimática
Citometria de Fluxo
Anticorpos Anti-HIV/sangue
Voluntários Saudáveis
Seres Humanos
Placebos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (Placebos)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186602


  9 / 10410 MEDLINE  
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[PMID]:29065122
[Au] Autor:Hake A; Pfeifer N
[Ad] Endereço:Department Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarland Informatics Campus, Saarbrücken, Germany.
[Ti] Título:Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time.
[So] Source:PLoS Comput Biol;13(10):e1005789, 2017 Oct.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/química
Anticorpos Neutralizantes/imunologia
Farmacorresistência Viral/imunologia
Mapeamento de Epitopos/métodos
Anticorpos Anti-HIV/química
Anticorpos Anti-HIV/imunologia
HIV-1/imunologia
[Mh] Termos MeSH secundário: Sítios de Ligação
Antígenos CD4
HIV-1/química
Seres Humanos
Ligação Proteica
Mapeamento de Interação de Proteínas/métodos
Análise de Sequência de Proteína/métodos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (HIV Antibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005789


  10 / 10410 MEDLINE  
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[PMID]:28994411
[Au] Autor:Gristick HB; Wang H; Bjorkman PJ
[Ad] Endereço:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
[Ti] Título:X-ray and EM structures of a natively glycosylated HIV-1 envelope trimer.
[So] Source:Acta Crystallogr D Struct Biol;73(Pt 10):822-828, 2017 Oct 01.
[Is] ISSN:2059-7983
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The structural and biochemical characterization of broadly neutralizing anti-HIV-1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures. 3.5 and 3.9 Šresolution crystal structures of the HIV-1 Env trimer with fully processed and native glycosylation were solved, revealing a glycan shield of high-mannose and complex-type N-glycans that were used to define the complete epitopes of two bNAbs. Here, the refinement of the N-glycans in the crystal structures is discussed and comparisons are made with glycan densities in glycosylated Env structures derived by single-particle cryo-electron microscopy.
[Mh] Termos MeSH primário: HIV-1/química
Manose/análise
Polissacarídeos/análise
Produtos do Gene env do Vírus da Imunodeficiência Humana/química
[Mh] Termos MeSH secundário: Anticorpos Neutralizantes/química
Microscopia Crioeletrônica
Cristalografia por Raios X
Glicosilação
Anticorpos Anti-HIV/química
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/ultraestrutura
Proteína gp41 do Envelope de HIV/química
Proteína gp41 do Envelope de HIV/ultraestrutura
Infecções por HIV/virologia
HIV-1/ultraestrutura
Seres Humanos
Modelos Moleculares
Conformação Proteica
Multimerização Proteica
Produtos do Gene env do Vírus da Imunodeficiência Humana/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp120); 0 (HIV Envelope Protein gp41); 0 (Polysaccharides); 0 (env Gene Products, Human Immunodeficiency Virus); PHA4727WTP (Mannose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1107/S2059798317013353



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