Expression data from a malaria vaccine trial (HG-U133A2.0 and U133 Plus 2.0)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE18323 | GEO | 2009/09/30
SECONDARY ACCESSION(S): PRJNA117977
REPOSITORIES: GEO
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Project description:Volunteers were assessed at study entry, the day of the third vaccination and 24, 72 hours, two weeks after vaccination, and 5 days after challenge. 13/39 vaccinees were protected and 26/39 were not protected. Eleven vaccinees exhibited delayed onset of parasitemia. All infectivity controls developed parasitemia. Prediction Analysis of Microarrays (PAM-R) identified genes corresponding with protection. Gene Set Enrichment Analysis (GSEA) identified sets of genes associated with protection after the third immunization, before challenge. After the third immunization, prior to challenge, differential expression of genes in the immunoproteasome pathway distinguished protected and non protected persons Experiment Overall Design: Samples were collected at study entry, the day of third vaccination, 24 and 72 hours post the third vaccination and two weeks post the third vaccination as well as 5 days post challenge. Both longitudinal and cross-sectional analysis were carried out to investigate expression profiles associated with vaccine effects and vaccine efficacy. This dataset contains 215 samples from HG-U133 A 2.0 platform and 39 samples from HG Plus2.0 platform.
2009-10-10 | E-GEOD-18323 | biostudies-arrayexpress
Project description:RTS,S is the sole candidate vaccine shown to provide protection against infection to malaria-naive adults challenged with mosquito-borne homologous falciparum malaria and protection against infection and clinical and severe disease to volunteers in malaria-endemic Africa who were exposed to diverse Plasmodium falciparum strains. In this experiment we profiled gene expression in PBMCs after vaccination with the RTS,S candidate malaria vaccine in a controlled human malaria infection study. Subjects were vaccinated with three doses of the RTS,S candidate malaria vaccine. Blood samples for PBMC isolation and subsequent gene expression analysis were taken on day 0 (0m), day of the third vaccination (8w), 1 day post third vaccination (8w1d), 3 days post third vaccination (8w3d), the day of the infection (10w), 1 day post infection (10w1d), and 5 days post infection (10w5d). After infection the subjects were closely monitored for parasitemia. The response to the controlled infection was recorded as follows: no parasitemia (P, protected), parasitemia in the same time frame as the control group (NP, not protected), parasitemia later than the control group (DL, delayed). In addition to the experimental factors, a confounding factor was identified in the data analysis related to the use of a specific kit batch (Kit A or B).
2017-04-27 | E-MTAB-4629 | biostudies-arrayexpress
Project description:We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. We immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses. For the protected RM, blood was collected before vaccination, on the day of first virus exposure and six weeks after last virus challenge. Lymph node and rectal pinch biopsies were performed before vaccination and six weeks after last virus challenge. Blood was collected in tempus tubes and processed immediately according to the manufacturer’s instructions and stored at -80C. The biopsy specimens were cut into small pieces and immediately placed into RNAlater solution (Qiagen, Valencia, CA) and also stored at -80C. Total RNA from blood, lymph node and rectal biopsies was extracted using RNAeasy extraction kits (Qiagen, Valencia, CA). cDNA labeling, hybridization, staining and scanning were performed according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA) for rhesus gene expression arrays.
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Project description:Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide and causes respiratory disease, abortion, and in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb at 4 to 6 days post-infection. Our previous results showed that EHV-1 KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks post-immunization, and that the infection with the attenuated KyA elicits protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of EHV-1 KyA by innate immune responses, CBA mice immunized with live KyA were challenged with RacL11 at various times post-vaccination. KyA immunization effectively protected CBA mice from RacL11 challenge at 1 to 7 days post-immunization. Immunized mice lost less than 10% of their preinfection body weight and rapidly regained body weight. Lung virus titers in EHV-1 KyA-immunized CBA mice were 1,000-fold lower at 2 days post-RacL11 challenge than lungs of non-immunized mice, which was indicative of accelerated virus clearance. Affymetrix microarray analysis revealed that IFN-γ and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h post-challenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γinhibited EHV-1 infection of murine alveolar macrophage MH-S cells and effectively protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression may be important in mediating protection elicited by KyA immunization. These results suggest that EHV-1 KyA can be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.
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Project description:Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with SIV peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenge with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on post-challenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral load five days after the first challenge, but which had unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant pre-challenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling enhances vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV.
2014-09-30 | GSE59068 | GEO
Project description:Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide. Intradermal (ID) vaccination with BCG has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission. Here we show that the route and dose of BCG vaccination alters circulating and lung resident T cells and subsequent protection against Mtb challenge in nonhuman primates (NHP). NHP immunized with BCG by the intravenous (IV) route induced substantially higher antigen-specific CD4 (Th1 or Th17) and CD8 responses in blood, spleen, bronchoalveolar lavage (BAL), and lung lymph nodes compared to the same BCG dose administered by ID or aerosol (AE) routes. Moreover, IV immunization was the only route that induced a high frequency of antigen-specific tissue resident T cells in lung parenchyma. Six months after BCG vaccination, NHP were challenged with virulent Mtb. Strikingly, 9 of 10 NHP that received BCG IV were highly protected, with 6 NHP showing no detectable infection as determined by PET CT imaging, mycobacterial growth, pathology, granuloma formation, or de novo immune responses to Mtb-specific antigens. The finding that BCG IV prevents or significantly limits Mtb infection in NHP has important implications for vaccine development and provides a model for determining immune correlates and mechanisms of protection against TB.
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Project description:Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with SIV peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenge with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on post-challenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral load five days after the first challenge, but which had unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant pre-challenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling enhances vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. 36 Indian-origin outbred, young adult, male and female rhesus macaques divided into thre vaccination groups of 12 animals each. Groups were balanced for Mamu-A*01 (three in each group), Mamu-B*08 (one in each group), and for susceptible and resistant TRIM5α alleles. There were no Mamu-B*17+ animals. The prime group (PG) received Gp96 SIV Ig vaccine 292 cells that were transfected with plasmids encoding gp96-Ig, SIVmac251 rev-tat-nef, Gag and gp160 (35). They were injected intraperitoneally with 107 irradiated gp96SIVIg vaccine cells in HBSS, which secrete 10 μg of gp96SIVIg per 24 h. For the prime-boost group (PBG), 100 g of rSIVgp120 protein was added to the vaccine cells. The control group received 292-gp96 Ig cells not transfected with SIV antigens. After a 32-week vaccination phase, which consisted of priming in weeks 0, 6, and 25 and (for the PBG only) additional boosts in weeks 6 and 25, all animals were subject to up to seven weekly low-dose intrarectal challenges starting at 33-week with SIVmac251 at a dosage of 120 TCID50. Whenever an animal had detectable viral load (>50 copies/ml of plasma) at 5 days post challenge, it was considered viremic, further challenges were suspended, and only viral load screening continued on a weekly basis. Whole blood samples (preserved in PAXgene tubes) were collected 2 weeks prior to the first prime, 1 week after the first prime, 2 weeks before and 1 week after the third prime, 1 week before the first challenge, for newly infected animals five days into the corresponding study week and from viremic animals four days into the study week (also denoted as challenge 2 and challenge 3). Total RNA was isolated from Paxgene tubes using Paxgene Blood RNeasy Mini Kits (Qiagen) following the manufacturer’s protocol. RNA quality was assessed on an Agilent 2100 Bioanalyzer using the nanochip format, and only intact RNA was used for microarray analyses.
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