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  1 / 1388 MEDLINE  
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[PMID]:29323855
[Au] Autor:Lebedev AV; Kazennova EV; Zverev SY; Nistratova YI; Laga VY; Tumanov AS; Glushchenko NV; Yarygina EI; Bobkova MR
[Ti] Título:Analysis of the env gene variability of the IDU-A HIV-1 variant in the outbreak of the HIV infection epidemic in Perm region of Russia (1996-2011).
[So] Source:Vopr Virusol;61(5):222-9, 2016.
[Is] ISSN:0507-4088
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:In the present work, a total of 132 HIV-1 env gene C2-V3-C3 sequences belonging to the IDU-A genetic variant were analyzed. The variants were obtained from the viruses circulating among IDUs and heterosexuals in the Perm region at different periods. It was shown that the rate of the divergence of the IDU-A HIV-1 viruses from a common ancestor increased 4.3 times (p < 0.001) in 2011 as compared with the onset of the epidemics. The rate of the HIV-1 evolution was different in the two risk groups of the infection. The mean genetic distance of HIV-1 variants circulating among heterosexuals was 1.3 times longer (p = 0.008) than that among IDUs. The accumulation rate of the nucleotide (including nonsynonymous) substitutions in the C2-V3-C3 HIV-1 env gene region among individuals infected by heterosexual contacts was 1.7 times higher than that among IDUs. The differences in the positions of the codons subjected to positive selection were demonstrated depending on the infection risk group tested.
[Mh] Termos MeSH primário: Surtos de Doenças
Variação Genética
Infecções por HIV/epidemiologia
HIV-1/genética
Abuso de Substâncias por Via Intravenosa/epidemiologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
[Mh] Termos MeSH secundário: Adulto
Códon
Feminino
Expressão Gênica
Infecções por HIV/transmissão
Infecções por HIV/virologia
HIV-1/classificação
Heterossexualidade
Seres Humanos
Masculino
Taxa de Mutação
Filogenia
Federação Russa/epidemiologia
Seleção Genética
Abuso de Substâncias por Via Intravenosa/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


  2 / 1388 MEDLINE  
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[PMID]:28743743
[Au] Autor:Kumar R; Ozorowski G; Kumar V; Holden LG; Shrivastava T; Patil S; Deshpande S; Ward AB; Bhattacharya J
[Ad] Endereço:From the HIV Vaccine Translational Research Laboratory, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, Haryana 121001, India.
[Ti] Título:Characterization of a stable HIV-1 B/C recombinant, soluble, and trimeric envelope glycoprotein (Env) highly resistant to CD4-induced conformational changes.
[So] Source:J Biol Chem;292(38):15849-15858, 2017 09 22.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The HIV-1 envelope (Env) is a glycoprotein consisting of a trimer of heterodimers containing gp120 and gp41 subunits that mediates virus entry and is a major target of broadly neutralizing antibodies (bnAbs) developed during infection in some individuals. The engagement of the HIV-1 gp120 glycoprotein to the host CD4 protein triggers conformational changes in gp120 that allow its binding to co-receptors and is necessary for virus entry to establish infection. Native-like HIV-1 Env immunogens representing distinct clades have been proposed to improve immunogenicity. In the present study, we examined the basis of resistance of an HIV-1 B/C recombinant Env (LT5.J4b12C) to non-neutralizing antibodies targeting CD4-induced Env epitopes in the presence of soluble CD4 (sCD4). Using native polyacrylamide gel shift assay and negative-stain EM, we found that the prefusion conformational state of LT5.J4b12C trimeric Env was largely unaffected in the presence of excess sCD4 with most Env trimers appearing to be in a ligand-free state. This resistance to CD4-induced conformational changes was associated with a lower affinity for CD4. Moreover, the LT5.J4b12C trimeric Env preferentially bound to the neutralizing antibodies compared with non-neutralizing antibodies. Taken together, we report on an HIV-1 B/C recombinant, native-like trimeric Env protein that is highly resistant to CD4-induced conformational changes but displays epitopes recognized by a diverse array of bnAbs. Such features make this B/C recombinant trimeric Env a useful addition to the pool of other recently identified native-like HIV-1 Env trimers suitable for use as antigenic bait for bnAb isolation, structural studies, and use as potential immunogens.
[Mh] Termos MeSH primário: Antígenos CD4/química
Antígenos CD4/farmacologia
HIV-1
Multimerização Proteica
Proteínas Recombinantes/química
Produtos do Gene env do Vírus da Imunodeficiência Humana/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Anticorpos Monoclonais/imunologia
Anticorpos Neutralizantes/imunologia
Antígenos CD4/metabolismo
Epitopos/imunologia
Células HEK293
Seres Humanos
Modelos Moleculares
Conformação Proteica
Estabilidade Proteica/efeitos dos fármacos
Estrutura Quaternária de Proteína
Proteínas Recombinantes/imunologia
Proteínas Recombinantes/metabolismo
Solubilidade
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (Epitopes); 0 (Recombinant Proteins); 0 (VRC01 monoclonal antibody); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.803056


  3 / 1388 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


  4 / 1388 MEDLINE  
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[PMID]:29023474
[Au] Autor:Kiwuwa-Muyingo S; Nazziwa J; Ssemwanga D; Ilmonen P; Njai H; Ndembi N; Parry C; Kitandwe PK; Gershim A; Mpendo J; Neilsen L; Seeley J; Seppälä H; Lyagoba F; Kamali A; Kaleebu P
[Ad] Endereço:Medical Research Council/Uganda Virus Research Institute, Research Unit on AIDS, Entebbe, Uganda.
[Ti] Título:HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach.
[So] Source:PLoS One;12(10):e0185818, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection. METHODS: Using data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering. RESULTS: Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00]) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40-11.68]). CONCLUSIONS: A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.
[Mh] Termos MeSH primário: Infecções por HIV
HIV-1/genética
Filogenia
Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Feminino
Infecções por HIV/epidemiologia
Infecções por HIV/genética
Infecções por HIV/transmissão
Seres Humanos
Lagos
Masculino
Meia-Idade
Uganda/epidemiologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (env Gene Products, Human Immunodeficiency Virus); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185818


  5 / 1388 MEDLINE  
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[PMID]:29020646
[Au] Autor:Joshi A; Cox EK; Sedano MJ; Punke EB; Lee RT; Maurer-Stroh S; Kaur P; Ng OT; Garg H
[Ad] Endereço:Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA. Electronic address: anjali.joshi@ttuhsc.edu.
[Ti] Título:HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites.
[So] Source:Virology;512:222-233, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HIV subtypes not only predominate in different geographical regions but also differ in key phenotypic characteristics. To determine if genotypic and/or phenotypic differences in the Envelope (Env) glycoprotein can explain subtype related differences, we cloned 37 full length Envs from Subtype B and AE HIV infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs have lower Potential N Glycosylation Sites and higher risk of ×4 development. Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells expressing low levels of CCR5. Moreover, the Maraviroc IC was higher for subtype B Envs and correlated with infectivity in low CCR5 expressing cells as well as PNGS. Specifically, the glycosylation site N301 in the V3 loop was seen less frequently in AE subtype and CXCR4 topic viruses. CRF01_AE differs from B subtype in terms of CCR5 usage and Maraviroc susceptibility which may have implications for HIV pathogenesis and virus evolution.
[Mh] Termos MeSH primário: Cicloexanos/farmacologia
HIV-1/classificação
Receptores CCR5/metabolismo
Triazóis/farmacologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Clonagem Molecular
Regulação Viral da Expressão Gênica/fisiologia
Glicosilação
HIV-1/genética
Seres Humanos
Modelos Moleculares
Conformação Proteica
Replicação Viral
Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCR5 protein, human); 0 (Cyclohexanes); 0 (Receptors, CCR5); 0 (Triazoles); 0 (env Gene Products, Human Immunodeficiency Virus); MD6P741W8A (maraviroc)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE


  6 / 1388 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


  7 / 1388 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


  8 / 1388 MEDLINE  
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[PMID]:28902916
[Au] Autor:Dubrovskaya V; Guenaga J; de Val N; Wilson R; Feng Y; Movsesyan A; Karlsson Hedestam GB; Ward AB; Wyatt RT
[Ad] Endereço:Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.
[Ti] Título:Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response.
[So] Source:PLoS Pathog;13(9):e1006614, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extensive shielding by N-glycans on the surface of the HIV envelope glycoproteins (Env) restricts B cell recognition of conserved neutralizing determinants. Elicitation of broadly neutralizing antibodies (bNAbs) in selected HIV-infected individuals reveals that Abs capable of penetrating the glycan shield can be generated by the B cell repertoire. Accordingly, we sought to determine if targeted N-glycan deletion might alter antibody responses to Env. We focused on the conserved CD4 binding site (CD4bs) since this is a known neutralizing determinant that is devoid of glycosylation to allow CD4 receptor engagement, but is ringed by surrounding N-glycans. We selectively deleted potential N-glycan sites (PNGS) proximal to the CD4bs on well-ordered clade C 16055 native flexibly linked (NFL) trimers to potentially increase recognition by naïve B cells in vivo. We generated glycan-deleted trimer variants that maintained native-like conformation and stability. Using a panel of CD4bs-directed bNAbs, we demonstrated improved accessibility of the CD4bs on the N-glycan-deleted trimer variants. We showed that pseudoviruses lacking these Env PNGSs were more sensitive to neutralization by CD4bs-specific bNAbs but remained resistant to non-neutralizing mAbs. We performed rabbit immunogenicity experiments using two approaches comparing glycan-deleted to fully glycosylated NFL trimers. The first was to delete 4 PNGS sites and then boost with fully glycosylated Env; the second was to delete 4 sites and gradually re-introduce these N-glycans in subsequent boosts. We demonstrated that the 16055 PNGS-deleted trimers more rapidly elicited serum antibodies that more potently neutralized the CD4bs-proximal-PNGS-deleted viruses in a statistically significant manner and strongly trended towards increased neutralization of fully glycosylated autologous virus. This approach elicited serum IgG capable of cross-neutralizing selected tier 2 viruses lacking N-glycans at residue N276 (natural or engineered), indicating that PNGS deletion of well-ordered trimers is a promising strategy to prime B cell responses to this conserved neutralizing determinant.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Anti-HIV/imunologia
Polissacarídeos/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Animais
Linfócitos B/imunologia
Antígenos CD4/imunologia
Ensaio de Imunoadsorção Enzimática
Epitopos de Linfócito B/imunologia
Feminino
HIV-1/imunologia
Imagem Tridimensional
Ativação Linfocitária/imunologia
Microscopia Eletrônica
Mutagênese Sítio-Dirigida
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (Epitopes, B-Lymphocyte); 0 (HIV Antibodies); 0 (Polysaccharides); 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:170914
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006614


  9 / 1388 MEDLINE  
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[PMID]:28835491
[Au] Autor:Wang Y; O'Dell S; Turner HL; Chiang CI; Lei L; Guenaga J; Wilson R; Martinez-Murillo P; Doria-Rose N; Ward AB; Mascola JR; Wyatt RT; Karlsson Hedestam GB; Li Y
[Ad] Endereço:Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA.
[Ti] Título:HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation. Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within a subset of individuals. To achieve this goal, an improved understanding of vaccine-elicited responses, including at the monoclonal Ab level, is essential. Here, we isolated and characterized a panel of vaccine-elicited cross-reactive neutralizing MAbs targeting the Env V3 loop that moderately neutralized several primary viruses and recapitulated the serum neutralizing antibody response. Striking similarities between the cross-reactive V3 NAbs elicited by vaccination in macaques and natural infections in humans illustrate commonalities between the vaccine- and infection-induced responses to V3 and support the feasibility of exploring the V3 epitope as a HIV-1 vaccine target in nonhuman primates.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Reações Cruzadas/imunologia
Anticorpos Anti-HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Macaca mulatta/imunologia
Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Epitopos/imunologia
Infecções por HIV/virologia
Seres Humanos
Imunização
Macaca mulatta/virologia
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (HIV Antibodies); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE


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



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