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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


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[PMID]:29385169
[Au] Autor:Bissa M; Forlani G; Zanotto C; Tosi G; De Giuli Morghen C; Accolla RS; Radaelli A
[Ad] Endereço:Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, Milan, Italy.
[Ti] Título:Fowlpoxvirus recombinants coding for the CIITA gene increase the expression of endogenous MHC-II and Fowlpox Gag/Pro and Env SIV transgenes.
[So] Source:PLoS One;13(1):e0190869, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells. Here, we report on construction of novel FPgp and FPenv recombinants that express the highly immunogenic SIV Gag-pro and Env structural antigens. Several FP-based recombinants, with single or dual genes, were also developed that express CIITA, driven from H6 or SP promoters. These recombinants were used to infect CEF and Vero cells in vitro and determine transgene expression, which was evaluated by real-time PCR and Western blotting. Subcellular localisation of the different proteins was evaluated by confocal microscopy, whereas HLA-DR or MHC-II expression was measured by flow cytometry. Fowlpox recombinants were also used to infect syngeneic T/SA tumour cells, then injected into Balb/c mice to elicit MHC-II immune response and define the presentation of the SIV transgene products in the presence or absence of FPCIITA. Antibodies to Env were measured by ELISA. Our data show that the H6 promoter was more efficient than SP to drive CIITA expression and that CIITA can enhance the levels of the gag/pro and env gene products only when infection is performed by FP single recombinants. Also, CIITA expression is higher when carried by FP single recombinants than when combined with FPgp or FPenv constructs and can induce HLA-DR cell surface expression. However, in-vivo experiments did not show any significant increase in the humoral response. As CIITA already proved to elicit immunogenicity by improving antigen presentation, further in-vivo experiments should be performed to increase the immune responses. The use of prime/boost immunisation protocols and the oral administration route of the recombinants may enhance the immunogenicity of Env peptides presented by MHC-II and provide CD4+ T-cell stimulation.
[Mh] Termos MeSH primário: Genes Virais
Complexo Principal de Histocompatibilidade/genética
Proteínas Nucleares/genética
Poxviridae/genética
Recombinação Genética
Vírus da Imunodeficiência Símia/genética
Transativadores/genética
Transgenes
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/genética
Vacinas contra a AIDS/imunologia
Animais
Western Blotting
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Linhagem Celular
Embrião de Galinha
Ensaio de Imunoadsorção Enzimática
Infecções por HIV/imunologia
Infecções por HIV/prevenção & controle
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Microscopia Confocal
Regiões Promotoras Genéticas
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (MHC class II transactivator protein); 0 (Nuclear Proteins); 0 (Trans-Activators)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190869


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[PMID]:29273432
[Au] Autor:Khrustalev VV; Khrustaleva TA; Kahanouskaya EY; Rudnichenko YA; Bandarenka HV; Arutyunyan AM; Girel KV; Khinevich NV; Ksenofontov AL; Kordyukova LV
[Ad] Endereço:Department of General Chemistry, Belarusian State Medical University, Dzerzinskogo 83, Minsk, Belarus. Electronic address: vvkhrustalev@mail.ru.
[Ti] Título:The alpha helix 1 from the first conserved region of HIV1 gp120 is reconstructed in the short NQ21 peptide.
[So] Source:Arch Biochem Biophys;638:66-75, 2018 01 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Investigations of short peptides that can be used in the next phase of synthetic HIV1 vaccine development are an urgent goal, as well as investigations of peptides that can be used in immunological tests with the aim to check the titer of antibodies against the alpha helix 1 from the first conserved region of HIV1 gp120 that are known to cause antibody-dependent cellular cytotoxicity (ADCC). The aim of this work was to study the structure of the NQ21 peptide corresponding to the less mutable part of the first conserved region of HIV1 gp120 (residues 94-114). The NQ21 peptide and its conjugate with biotin (biotin-NQ21) are absolutely alpha-helical in phosphate buffer solutions at pH = 6.8, 7.4 and 8.0, as well as in the dried form, according to the results of surface-enhanced Raman scattering (SERS) spectroscopy. Results of the native gel electrophoresis and thermal analysis under the control of spectrofluorometer and near UV circular dichroism (CD) showed that the peptide exists in form of octamers and tetramers at pH = 7.4, that is important information for further vaccine development. Strong signal of interacting Trp residues in oligomers in the far UV CD obscures the signal from secondary structure, but becomes less intensive during the heating.
[Mh] Termos MeSH primário: Proteína gp120 do Envelope de HIV/química
HIV-1/química
Peptídeos/química
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/química
Dicroísmo Circular
Concentração de Íons de Hidrogênio
Estrutura Secundária de Proteína
Análise Espectral Raman
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (HIV Envelope Protein gp120); 0 (Peptides); 0 (gp120 protein, Human immunodeficiency virus 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


  4 / 7322 MEDLINE  
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[PMID]:28448594
[Au] Autor:Borthwick N; Lin Z; Akahoshi T; Llano A; Silva-Arrieta S; Ahmed T; Dorrell L; Brander C; Murakoshi H; Takiguchi M; Hanke T
[Ad] Endereço:The Jenner Institute, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines.
[So] Source:PLoS One;12(4):e0176418, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8+ T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes. The less variable, more protective epitopes in conserved regions are typically subdominant. Therefore, induction of strong responses to conserved regions by vaccination provides an opportunity to discover novel important epitopes. METHODS: Cryopreserved lymphocytes from vaccine recipients were expanded by stimulation with 15-mer responder peptides for 10 days to establish short term-cell-line (STCL) effector cells. These were subjected to intracellular cytokine staining using serially truncated peptides and peptide-pulsed 721.221 cells expressing individual HLA class I alleles to define minimal epitope length and HLA restriction by stimulation of IFN-γ and TNF-α production and surface expression of CD107a. RESULTS: Using lymphocyte samples of 12 vaccine recipients, we defined 14 previously unreported optimal CD8+ T-cell HIV-1 epitopes and their four-digit HLA allele restriction (6 HLA-A, 7 HLA-B and 1 HLA-C alleles). Further 13 novel targets with incomplete information were revealed. CONCLUSIONS: The high rate of discovery of novel CD8+ T-cell effector epitopes warrants further epitope mining in recipients of the conserved-region vaccines in other populations and informs development of HIV-1/AIDS vaccines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01151319.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Linfócitos T CD8-Positivos/imunologia
Sequência Conservada
Infecções por HIV/prevenção & controle
HIV-1/imunologia
HIV-1/fisiologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/química
Alelos
Sequência de Aminoácidos
Epitopos de Linfócito T/química
Epitopos de Linfócito T/imunologia
Infecções por HIV/genética
Antígenos HLA/genética
Seres Humanos
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (HLA Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176418


  5 / 7322 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


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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


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[PMID]:29052689
[Au] Autor:Fauci AS
[Ad] Endereço:National Institute of Allergy and Infectious Diseases at the National Institutes of Health, Bethesda, Maryland.
[Ti] Título:An HIV Vaccine Is Essential for Ending the HIV/AIDS Pandemic.
[So] Source:JAMA;318(16):1535-1536, 2017 Oct 24.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Vacinas contra a AIDS
Infecções por HIV/prevenção & controle
Pandemias/prevenção & controle
[Mh] Termos MeSH secundário: Síndrome de Imunodeficiência Adquirida/prevenção & controle
Fármacos Anti-HIV/uso terapêutico
Saúde Global
Infecções por HIV/tratamento farmacológico
Infecções por HIV/epidemiologia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Anti-HIV Agents)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.13505


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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


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[PMID]:28953921
[Au] Autor:Rosás-Umbert M; Mothe B; Noguera-Julian M; Bellido R; Puertas MC; Carrillo J; Rodriguez C; Perez-Alvarez N; Cobarsí P; Gomez CE; Esteban M; Jímenez JL; García F; Blanco J; Martinez-Picado J; Paredes R; Brander C
[Ad] Endereço:IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain.
[Ti] Título:Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B.
[So] Source:PLoS One;12(9):e0184929, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Infecções por HIV/imunologia
Infecções por HIV/prevenção & controle
HIV-1/fisiologia
Vacinação
[Mh] Termos MeSH secundário: DNA Viral/metabolismo
Infecções por HIV/virologia
HIV-1/imunologia
Seres Humanos
Imunidade Humoral
Resultado do Tratamento
Carga Viral/imunologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (DNA, Viral)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184929


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[PMID]:28880880
[Au] Autor:Nyaoke BA; Mutua GN; Sajabi R; Nyasani D; Mureithi MW; Anzala OA
[Ad] Endereço:KAVI -Institute of Clinical Research (KAVI-ICR), University of Nairobi. Nairobi, Kenya.
[Ti] Título:Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya.
[So] Source:PLoS One;12(9):e0183788, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: 1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as 'advancing research' and collaboration with science, and personal benefits such as health benefits and financial interests. METHOD: A thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site. RESULTS: Of the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research. CONCLUSION: The majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine clinical trials.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Ensaios Clínicos como Assunto
Motivação
Voluntários
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Demografia
Escolaridade
Feminino
Seres Humanos
Quênia
Masculino
Participação do Paciente
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183788



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