Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Macaca mulatta
PROVIDER: GSE73654 | GEO | 2015/10/02
SECONDARY ACCESSION(S): PRJNA297509
REPOSITORIES: GEO
Similar Datasets
Project description:Mice were left unvaccinated (Naive) or vaccinated with either BCG alone (BCG) or BCG followed by two intranasal boosting of novel nanovaccines Nano-FP1 or Nano-FP2, 12 and 14 weeks later. A group of mice were also administered a 3rd boost of the corresponding nanovaccine 25 weeks after sc. BCG. Mice were sacrificed at 2, 11 and 14 weeks after second boosting, and bronchoalveolar lavage (BAL) and lung parenchyma (Lung) were extracted for RNA-Seq. The group of mice administered a 3rd boosting was the group sacrificed at 14 weeks time-point.
2021-01-28 | E-MTAB-9449 | biostudies-arrayexpress
Project description:Gene expression profiles in PPD-stimulated and unstimulated peripherhal blood mononuclear cells isolated from chinese cynomolgus macaques before and after BCG vaccination and before and after M. tuberculosis challenge were compared in animals able to control TB infection and those that developed TB disease in order to identify potential correlates of protection and/or biomarkers of disease. 6 macaques received BCG vaccination prior to challenge and were able to control TB infection (vaccinated controllers). 3 unvaccinated macaques were also able to control TB infection after challenge (unvaccinated controllers) and 3 other unvaccinated macaques developed TB disease and reached humane endpoint criteria (unvaccinated progressors). PBMCs isolated at 8 and 18 weeks post BCG-vaccination from the vaccinated controllers and at 6 weeks post M.tb challenge and at 2 time-points when the animals were naive in all animals were stimulated with PPD. RNA was extracted from the cells and hybridised to and Agilent rhesus macaque GE microarray in a one-colour hybridisation. Gene expression post-vaccination and/or post-challenge was compared with expression before vaccination/challenge when the animals were naive.
2012-11-15 | E-GEOD-42273 | biostudies-arrayexpress
Project description:Tuberculosis (TB) is a global pandaemic, partially due to the failure of vaccination approaches. Novel anti-TB vaccines are therefore urgently required. Here we show that aerosol immunization of macaques with the Mtb mutant in SigH (MtbΔsigH) results in significant recruitment of inducible bronchus-associated lymphoid tissue (iBALT) as well as CD4(+) and CD8(+) T cells expressing activation and proliferation markers to the lungs. Further, the findings indicate that pulmonary vaccination with MtbΔsigH elicited strong central memory CD4(+) and CD8(+) T-cell responses in the lung. Vaccination with MtbΔsigH results in significant protection against a lethal TB challenge, as evidenced by an approximately three log reduction in bacterial burdens, significantly diminished clinical manifestations and granulomatous pathology and characterized by the presence of profound iBALT. This highly protective response is virtually absent in unvaccinated and BCG-vaccinated animals after challenge. These results suggest that future TB vaccine candidates can be developed on the basis of MtbΔsigH.
| S-EPMC4608260 | biostudies-literature
Project description:Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.
2022-06-11 | GSE201530 | GEO
Project description:Micro RNA profiling was performed on in vitro PPDB and nil stimulated bovine PBMCs isolated from BCG vaccinated and unvaccinated cattle before and after challenge with M. bovis.
2014-06-01 | E-MTAB-2291 | biostudies-arrayexpress
Project description:Purpose: Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. Methods: In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Results: Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. Conclusions: These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.
2021-03-10 | GSE164649 | GEO
Project description:The aim of the project was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB. The latter situation may be determined if Latent patients have a blood transcriptional signature similar to that in Active patients. The transcriptional signature in Active TB patients may also provide information as to the factors leading to immunopathogenesis, thus possibly identifying therapeutic targets. The transcriptional profile in Latent TB may give information as to the protective factors controlling the infection, thus important for monitoring vaccine development. A further aim was to examine the transcriptional blood profile of active TB patients at the time of recruitment (before drug treatment) and then subsequently at specific time points after drug treatment to determine whether the signature is extingsuihed with treatment and when. London is a site of intermediate burden of TB - the study was initiated in London, across a broad range of ethnicities to obtain a robust signature that could be used in different developing countries where there is a high burden TB disease. Experimental design : Whole blood collected in tempus tubes from patients with different spectra of TB disease and healthy controls. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum or bronchoalvelolar lavage fluid. Latent TB: LTB - All patients were screened at a tuberculosis clinic, being either new entrants to the UK from endemic countries or being household contacts of infectious cases. All were positive by tuberculin skin test (>14mm if BCG vaccinated, >5mm if not vaccinated) and were also positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Latent patients had no clinical, radiological or microbiological evidence of active infection and were asymptomatic. Healthy controls - these were volunteers without exposure to TB who were negative by both tuberculin skin test (<15mm if BCG vaccinated, <6mm if unvaccinated); who were also negative by IGRA (as described above). In this dataset: PTB n= 13; LTB n = 17; BCG+ n = 6, BCG-, n =6. Experimental variables : Patient group: Active PTB; Latent TB, Healthy controls (BCG vaccinated and unvaccinated). ethnicity - a wide range of ethnic groups is represented. However all controls in this dataset are broadly Caucasian/White. The active PTB group incorporates a range of smear positive and smear negative disease and a spectrum of disease extent/severity.
2010-08-11 | E-GEOD-19439 | biostudies-arrayexpress
Project description:The aim of this study was to measure the immune response of alveolar macrophages (AMs) from BCG-vaccinated mice to intracellular Mtb infection in vivo. We characterized the transcriptional profile of murine Mtb-infected AMs after aerosol infection by sorting cells from bronchoalveolar lavage fluid and performing low-input RNA-sequencing.
2023-11-30 | GSE212202 | GEO
Project description:In this study we attempt to elucidate some of the pathways involved in the immune response to vaccination and subsequent disease challenge using a transcriptomic approach. We exposed, via intra-peritoneal injection, three months old Asian seabass (Lates calcarifer) to a Streptococcus iniae vaccine. A control group was also set up where no vaccine was injected. Spleen and head kidney samples were collected at one and seven days post vaccination for transcriptomic analysis. At this point, there are four groups per organ: Day 1 vaccinated, Day 1 control, Day 7 vaccinated and Day 7 control. Subsequently, a pathogen challenge was carried out three weeks later and spleen and head kidneys were sampled at 25-29 hours post challenge for transcriptomic analysis. For control, mock challenged was carried out. At this point, there are four groups per organ: unvaccinated challenged, unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged. Total 57 samples. Spleen samples: At Day 1 and Day 7 post vaccination, 4 spleens were analyzed for each of the D1 control and D1 vaccinated groups and 3 spleens were analyzed for each of the D7 control and D7 vaccinated groups (total = 14 samples). At post pathogen challenge, 4 spleens were analyzed for each of these three groups - unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged and 3 spleens for the unvaccinated challenged group (total = 15 samples). Head Kidney samples: At Day 1 and Day 7 post vaccination, 3 head kidneys were analyzed for the control and vaccinated groups for both time points (total = 12 samples). At post pathogen challenge, 4 head kidneys were analyzed for each of the groups: unvaccinated challenged, unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged (total = 16 samples).
2014-10-01 | E-GEOD-51839 | biostudies-arrayexpress
Project description:Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTM), a distinct lineage from Mtb, are opportunistic pathogens present in the environment. TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy. Therefore, we developed a mouse model (BCG+NTM) that mimics human BCG vaccination at an early stage and continuous NTM exposure via the oral route, including during TB infection. Our results show that BCG+NTM mice had improved protection against pulmonary TB correlating with increased pulmonary influx of B-cells, higher titers of anti-Mtb IgA and IgG antibodies in serum and airways, compared to mice vaccinated with BCG alone. Notably, the lungs of BCG+NTM mice developed B-cell aggregates expressing markers of germinal center formation as determined by spatial transcriptomics. We conclude a direct correlation between NTM exposure and protection from TB, with B-cells playing a crucial role.
2022-10-23 | GSE203037 | GEO