Long-Term Programming of Antigen-Specific Immunity from Gene Expression Signatures in the PBMC of Rhesus Macaques Immunized with an SIV DNA Vaccine
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE35816 | GEO | 2012/02/15
SECONDARY ACCESSION(S): PRJNA152149
REPOSITORIES: GEO
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Project description:The primary objective of this study was to evaluate response to a SIV DNA-based vaccine that was adminstered via vivo electroporation (EP) in rhesus macaques to further understand the molecular correlates of protection against SIV. In this study, rhesus macaques were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES), followed by EP. At eight month post-vaccination, animals were challenged with SIV. Standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis were performed to determine the host response to each vaccine regimen. The overall study was designed to evaluate the response to a SIV-DNA vaccination administered to animals via intramuscular electroporation. Chinese rhesus macaques were divided into three treatment groups (n=6 animals per group): Control (no vaccination), DNA vaccine alone (pCSIVgag, pCSIVpol, pCSIVenv), DNA vaccine with RANTES adjuvant (pCSIVgag, pCSIVpol, pCSIVenv, pmacRANTES). Eight months following the last vaccination, animals were infected with 25 MID of SIVmac251 and response to infection was monitored. RNA for microarray analysis was isolated from fresh PBMCs that were isolated from individual animals and treated overnight with a pool of overlapping SIV pol peptides or mock treated. Samples for microarray analysis were taken longitudinally at 8 months post-vaccination (pre-SIV challenge; biological n=5-6 per group for each treatment; technical n=2 for each sample) and at day 10 post-SIV challenge (n=5-6 per group for each treatment; technical n=2 for each sample).
2012-02-15 | E-GEOD-35816 | biostudies-arrayexpress
Project description:An efficacious vaccine to HIV-1 remains elusive. We tested two vaccine regimens based on prime-boosting with two chimpanzee-origin adenovirus (Ad) vectors (SAdV) of serotypes SAdV24 and SAdV23 or two distinct human serotype Ad vectors (HAdV), i.e., HAdV5 and HAdV26, expressing Gag and gp160 of SIVmac239 for induction of protection against repeated low dose rectal SIVmac251 challenges in Indian rhesus macaques (RMs). Animals were rendered seropositive to the HAdV vectors prior to vaccination. In RMs with non-controller genotypes, the SAdV vectors achieved significant reduction in viral acquisition. In RMs with controller genotypes, both vaccine regimens reduced set-point and peak viral loads and accelerated viral clearance. In SAdV-vaccinated RMs resistance against infection correlated with levels of circulating envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads upon infection. Circulating CD4+ and CD8+ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+ T cells may play a role in protection. Our results demonstrate that SAdV-based candidate AIDS vaccines provide protection from virus acquisition and replication in a stringent SIV challenge model in RMs and may thus outperform HIV-1 vaccines that have undergone large-scale clinical efficacy testing in humans.
2019-05-21 | GSE102115 | 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:SIVmac239Δnef (SIVΔnef) live attenuated vaccine (LAV) induces the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. Time-dependent protection is a unique feature of this vaccine: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. To elucidate the protection mechanisms induced by SIVΔnef vaccine, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01 rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in cell activation, differentiation and maturation toward central memory cells. Our study indicates that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time may contribute to the maturation of time dependent protection.
2015-12-02 | GSE75567 | GEO
Project description:Lassa fever (LF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs of virulent disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of AIDS. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, weight loss, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections included increased expression of interferon response genes and decreased expression of COX2, IL-1?, coagulation intermediates and nuclear receptors needed for stress signaling. Here it is demonstrated that SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and that none developed signs of arenavirus disease or persistence. Furthermore, 5 of 5 animals given a heterologous challenge with a lethal dose of LCMV-WE survived without developing disease signs. 30 RNA samples from Monkey PBMC: 4 uninf. Monkey PBMC, 8 SIV-infected Monkey PBMC(From 8 Monkeys), 5 SIV+ML29-sc infected week1(Monkey PBMC), 5 SIV+ML29-sc infected week2(Monkey PBMC), 1 SIV+ML29-ig infected week1(Monkey PBMC), 1 SIV+ML29-ig infected week2(Monkey PBMC), 2 SIV+Arm-sc infected week1(Monkey PBMC), 2 SIV+Arm-sc infected week2(Monkey PBMC), 1 only ML29-iv infected week1(Monkey PBMC), 1 only ML29-iv infected week2(Monkey PBMC)
2013-11-04 | E-GEOD-33687 | biostudies-arrayexpress
Project description:Question Addressed: Does gene expression change in the buccal mucosa of Lymphocryptovirus (LCV) infected animals when they are chronically infected with Simian immunodeficiency virus (SIV)? Oropharyngeal mucosal tissue samples were collected from rhesus macaques. A pooled common reference was used for all hybridizations. This reference was composed of RNA harvested from rhesus macaques not infected with either LCV or SIV. Infection: Animals were infected with SIV and/or LCV
2024-05-24 | GSE38918 | GEO
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Project description:Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing.
2016-01-22 | GSE72766 | GEO
Project description:Impact of CD8 depletion on peripheral CD4+ T cells transcriptome during ART-treated SIV infection of rhesus macaques. Analysis of CD8+ T cells, CD4+ T cells, and NK cell transcriptomes following administration of HIV/SIV latency reversing agent IL-15 superagonist N-803 in ART-suppressed SIV infected rhesus macaques. Methods: RNA-Seq of sorted CD4+ T cells from SIV-infected, ART-suppressed rhesus macaques before intervention with the anti-CD8a depleting antibody MT807R1 and then again on day 3, week 2, and week 4 following the start of intervention. Some animals also had an intervention that includes four weekly administrations of the IL-15 superagonist complex N-803 initiated at the time of CD8 depletion. Methods: RNA-Seq of sorted CD4+ T cells, CD8+ T cells, and NK cells from SIV-infected, ART-suppressed rhesus macaques before intervention with four weekly administrations of the IL-15 superagonist complex N-803, then again on day 3, week 2, and week 4 following the start of intervention. Methods: RNA from sorted cells was collected and extracted and DNA was digested. Libraries were prepared and normalized, pooled, and clustered on a flow cells for sequencing. RNAseq data were aligned to the MacaM v7.8 assembly of the Indian rhesus macaque genome. To identify pathways differentially modulated, Gene Set Enrichment Analysis (GSEA)34 was performed on the ranked transcript lists using 1000 phenotype permutations and random seeding. Gene sets used included the MSigDB H (hallmark) gene sets
2020-01-06 | GSE128415 | 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