Ontology highlight
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PROVIDER: PRJNA1313015 | ENA |
REPOSITORIES: ENA
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Project description:Comparison of expression levels of the genes on chromosome 22 in the peripheral blood mononuclear cells at various time points after stimulation with HIV-gag and env peptides
2008-10-31 | E-TABM-571 | biostudies-arrayexpress
Project description:The HIV-1 surface glycoprotein Env binds target receptors to mediate fusion of the viral and host cell membranes during infection. Env is incorporated with very low density into virions, and in some cell types, regions within the long cytosolic C-terminal tail may mediate direct or indirect associations with Gag during virus assembly and budding. Here, the mutational landscape is determined across the transmembrane and proximal cytosolic domains of Env (001428 isolate from clade C) interacting with the MA domain of Gag at cellular membranes. No evidence is found in a derivative line of HEK293 cells for specific motifs that mediate Env/MA associations.
2019-02-07 | GSE126136 | GEO
Project description:Attenuated poxviruses are safe and capable to express foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and direct and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. RNA expression obtained from DCs infected by NYVAC-C-dB19R and NYVAC-C-KC-dB19R compared to RNA expression obtained from DCs infected by NYVAC-C Supplementary file 'normalized_data_Human_V3_V2.txt' reports data for ILMN identifiers common to platforms HumanRef8V2 and HumanRef8V3.
2010-12-21 | E-GEOD-26239 | biostudies-arrayexpress
Project description:All lentiviral vectors derived from HIV-1 have the major splice donor (SD1) in the 5’ leader region and splice acceptor 7 (SA7) within the env region. Splicing events decrease the amount of full-length RNA available for packaging into virions and could lead to packaging of genomes containing internal deletions. Because there are splice sites or splicing enhancer/silencer elements in both gag and env, we compared how deleting each region affected intracellular genomic RNA splicing in RNA isolated from transfected HEK293Tsa cells. Oxford Nanopore direct cDNA sequencing was used to characterize the splice variants because the long-read length allows full-length transcripts to be analyzed. We show that deleting 507 nt of env, including the SA7, decreased the number of splicing events per transcript and increased the proportion of unspliced genomic RNAs ~3-fold in the cell.
2021-01-30 | GSE165829 | GEO
Project description:Attenuated poxviruses are safe and capable to express foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and direct and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.
2010-12-21 | GSE26239 | GEO
Project description:Heterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T-cell responses. In this phase I/II multi-arm trial, three vaccine candidates were used as prime or boost: MVA HIV-B (coding for Gag, Pol, Nef); HIV LIPO-5 (5 lipopeptides from Gag, Pol, Nef); DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, Env gp160 clade B). Healthy volunteers (n=92) were randomized to four groups: 1) MVA at weeks (W) 0/8 + LIPO-5 at W20/28 (M/L); 2) LIPO-5 at W0/8 + MVA at W20/28 (L/M); 3) DNA at W0/4/12 + LIPO-5 at W20/28 (G/L); 4) DNA at W0/4/12 + MVA at W20/28 (G/M). Frequency of IFNγ-ELISpot responders at W30 was 33%, 43%, 0% and 74%, respectively. Only MVA-receiving groups were further analyzed. Gene expression profiles of 79 subjects at different timepoints were analyzed by Illumina Whole-Genome Gene Expression BeadChips. Significant whole blood gene expression changes were observed two weeks after the first MVA injection, regardless of its use as prime or boost. An MVA gene signature was identified, including 86 genes mainly related to cell cycle pathways. Three prime-boost strategies led to CD4+ and CD8+ T cell responses and to a whole blood gene expression signature primarily due to their MVA HIV-B component.
2022-04-15 | GSE196172 | GEO
Project description:Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy chain complementarity-determining region 3 (HCDR3), suggesting that rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bind inferred germlines for PCT64 and PG9 and have higher affinities for bnAbs; determined cryo-EM structures of ApexGT trimers bound to inferred germline and bnAb forms of PCT64 and PG9; and developed an mRNA-encoded cell-surface trimer for our lead ApexGT candidate. The methods and immunogens developed here have promise to assist the development of an HIV vaccine.
2023-03-11 | PXD033766 | Pride
Project description:The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunisation of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunised with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.
2022-07-21 | GSE179513 | GEO
Project description:System immunology was used to identify the mechanisms linked to the immunogenicity and protective efficacy of an HIV vaccine comprised of Env and Gag DNA and Env proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA and protein in contralateral sites in female rhesus macaques. Interestingly, only macaques in the co-administration vaccine group were protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and showed 67% risk reduction per exposure. Macaques in the co-administration group developed higher migratory monocytes (CXCR4+ monocytes with increased LYN expression) from blood to lymph nodes. The heightened frequency of those migratory monocytes was associated with heightened ADCC pre-challenge and with decreased risk of acquisition. These data suggest that monocytes migration is key to the simultaneous recognition, processing and presentation of DNA+Env protein in the same draining lymph nodes to confer protective immunity.
2025-09-02 | GSE307016 | GEO
Project description:System immunology was used to identify the mechanisms linked to the immunogenicity and protective efficacy of an HIV vaccine comprised of Env and Gag DNA and Env proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA and protein in contralateral sites in female rhesus macaques. Interestingly, only macaques in the co-administration vaccine group were protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and showed 67% risk reduction per exposure. Macaques in the co-administration group developed higher migratory monocytes (CXCR4+ monocytes with increased LYN expression) from blood to lymph nodes. The heightened frequency of those migratory monocytes was associated with heightened ADCC pre-challenge and with decreased risk of acquisition. These data suggest that monocytes migration is key to the simultaneous recognition, processing and presentation of DNA+Env protein in the same draining lymph nodes to confer protective immunity.
2025-09-29 | GSE309509 | GEO