Ontology highlight
ABSTRACT:
PROVIDER: PRJNA427906 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Here we applied a systems approach to define human innate immune signatures following MRKAd5/HIV immunization and to analyze the effects of pre-existing Ad5 immunity. We defined the global early immune response to MRKAd5/HIV by profiling the PBMC transcriptomes from seven Ad5Neg individuals pre- and post-vaccination in vivo. Since the Step Study results suggested a deleterious effect of pre-existing Ad5 nAb on vaccine immunogenicity, we examined the vaccine-induced transcriptional responses from two Ad5Med and one Ad5Low individual 50 total samples were analyzed. This includes 5 time points post vaccination with MRKAd5/HIV for 10 independent human subjects. The time points were 0hr, 6hrs, 24hrs, 72hrs, and 168hrs. Seven of the subjects did not have pre-existing neutralizing antibodies to the vaccine vector (Ad5Neg). One subject had low level pre-existing neutralizing antibodies to the vaccine vector (Ad5Low). Two subjects had moderate level pre-existing neutralizing antibodies to the vaccine vector (Ad5Low).
2012-11-20 | E-GEOD-22768 | biostudies-arrayexpress
Project description:We sought to determine differences in transcript expression between a cohort of HIV-infected individuals that either developed broadly neutralizing antibodies (bnAb) or did not develop them (control). With the ultimate goal to identify transcripts that are associated with the development of bnAbs that would identify novel pathways that could be targeted in future vaccine strategies to increase the frequency of individuals that develop bnAbs against HIV. Using this approach we identified that Rab11 recycling endosomes, particularly in dysfunctional natural killer cells are associated with the development of HIV-1 bnAbs.
2018-11-01 | GSE115449 | GEO
Project description:The goal of an effective AIDS vaccine is to generate immunity that will prevent HIV-1 acquisition. Despite limited progress towards this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime/rAd5 boost vaccination with SIVmac239 Gag/Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8+ T cells showed strong virus inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells. The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection.
2012-06-15 | GSE35628 | GEO
Project description:Understanding why some indidivual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline and after antigenic stimulation in HIV-1 resistant commercial sex-workers from Nairobi, Kenya to HIV-1 low-risk negative (non-resistant) non-commercial sex-workers using immune-focused gene expression arrays Keywords: Case-control, disease state analysis CD4+ T cells from both HIV resistant and HIV low-risk negative individuals were isolated from PBMC after 24 hours of culture by negative slelction. Total RNA was isolated and gene expression compared using immune-focused expression arrays.
2010-03-01 | E-GEOD-14279 | biostudies-arrayexpress
Project description:Understanding why some indidivual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline and after antigenic stimulation in HIV-1 resistant commercial sex-workers from Nairobi, Kenya to HIV-1 low-risk negative (non-resistant) non-commercial sex-workers using immune-focused gene expression arrays Keywords: Case-control, disease state analysis
2010-03-02 | GSE14279 | GEO
Project description:The goal of an effective AIDS vaccine is to generate immunity that will prevent HIV-1 acquisition. Despite limited progress towards this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime/rAd5 boost vaccination with SIVmac239 Gag/Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8+ T cells showed strong virus inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells. The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection. Gag CM9-specific EM CD8+ T cells (CD28 low CD95 high tetramer+) from SIV-negative macaques at 12 wks post-DNA/rAd5 immunization were sorted by flow cytometry for microarray studies. RNA samples from strong VIA animals with (n=3) or without (n=6) CM9 peptide stimulation, along with CM9 peptide stimulated samples from weak VIA animals (n=2) were prepared using the Illumina beads station assay and hybridized to the Illumina HumanHT-12 version 4 Expression BeadChip.
2012-06-14 | E-GEOD-35628 | biostudies-arrayexpress
Project description:Despite the critical role antigen-specific T cells play in containing viral infections, their aggregate frequencies in peripheral blood have not correlated with clinical protection during HIV infection. However, a subset of HIV-specific T cells, which are capable of simultaneously producing multiple effector cytokines, termed polyfunctional T cells, have correlated with delayed disease progression. HIV-specific polyfunctional T cells have been enumerated and characterized using the intracellular cytokine staining (ICS) assay, which allows for simultaneous multiplexed analysis of cytokine expression at the single-cell level. In addition, using an unbiased computational analysis of ICS data generated through the RV144 HIV vaccine case-control study, we identified vaccine-induced HIV envelope (Env)-specific polyfunctional CD4 T cells as a novel correlate of reduced risk of HIV infection. However, very little is known about these cells and what differentiates them from other vaccine-elicited T cells. In addition, the use of sample fixation in the ICS assay prevents those cells from being further interrogated for transcriptional differences. Thus, we developed a novel live-cell multiplexed cytokine capture assay which allows for identification, sorting and transcriptional profiling of individual antigen-specific polyfunctional T cells by single-cell RNA-sequencing (scRNA-seq). We applied these methods to peripheral blood samples from participants who had received the RV144 vaccine regimen as part of the HVTN 097 clinical trial. Using this approach, we discovered transcriptional signatures that specifically identify the single-cell Env-specific CD4 T-cell functional profiles which had correlated with reduced risk of HIV infection in RV144. Interestingly, this signature is particularly characterized by upregulation of Th2 cytokines, supporting the hypothesis that the vaccine-induced Env-specific CD4 T cells likely contributed to the reduced risk of infection by providing T cell help to the Env-specific antibody responses. By interrogating the gene signatures that correlated with polyfunctionality, we have identified potential mechanisms of how vaccine-elicited polyfunctional T cells may contribute to reduced risk of HIV infection.
2022-05-25 | GSE166945 | GEO
Project description:Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. Vaccine was dosed to induce binding antibody titers against ancestral spike, but not efficient virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post infection reflects both vaccination status and disease course, and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of neutralizing antibodies, correlates with recall of broadly reactive B- and T-cell responses.
2023-12-18 | GSE246866 | GEO