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To compare the expression profile of CD8 T cells from mice vaccinated with Ad85A via the intranasal (IN) or intradermal (ID) routes isolated from lungs or spleen.

ABSTRACT: In Balb/c mice, the presence of effector CD8 T cells in lungs after intra-nasal (IN) immunization with replication deficient recombinant Adenovirus expressing the 85A antigen from Mycobacterium tuberculosis (MTb) (Ad85A) correlates with protection against aerosol MTb infection. In order to identify differentially expressed transcripts which contribute to protection by IN immunized lung CD8 T cells, total RNA from CD8 T cells isolated from target tissue (lungs) and lymphoid organ (spleen ) after a protective (IN) and non-protective (intradermal, ID) immunization regime will be analyzed in a whole-genome microarray study.

ORGANISM(S): Mus musculus

PROVIDER: GSE23713 | GEO | 2010/08/24

SECONDARY ACCESSION(S): PRJNA130877

REPOSITORIES: GEO

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To compare the expression profile of CD8 T cells from mice vaccinated with Ad85A via the intranasal (IN) or intradermal (ID) routes isolated from lungs or spleen.

Project description:In Balb/c mice, the presence of effector CD8 T cells in lungs after intra-nasal (IN) immunization with replication deficient recombinant Adenovirus expressing the 85A antigen from Mycobacterium tuberculosis (MTb) (Ad85A) correlates with protection against aerosol MTb infection. In order to identify differentially expressed transcripts which contribute to protection by IN immunized lung CD8 T cells, total RNA from CD8 T cells isolated from target tissue (lungs) and lymphoid organ (spleen ) after a protective (IN) and non-protective (intradermal, ID) immunization regime will be analyzed in a whole-genome microarray study. Total RNA from CD8 T cells isolated from lungs or spleens of Balb/c mice 3 weeks post-immunization with Ad85A through the IN (protective) or ID (non-protective) route will be compared.

2010-08-24 | E-GEOD-23713 | biostudies-arrayexpress

A Ferritin Mutant Induces Protective Immunity against Virulent Mycobacterium tuberculosis Infection

Project description:Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with ?bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the ?bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the ?bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the ?bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB. Female C57BL/6 mice were vaccinated subcutaneously with ?bfrB or BCG . At 8 weeks post-vaccination, mice were aerosol infected with Mtb H37Rv. At 4 weeks post infection, mice were sacrificed and lungs were removed. Lung total RNA from vaccinated and Mtb-infected mice was extracted, purified and were processed separately for microarray analysis.

2014-09-01 | E-GEOD-58810 | biostudies-arrayexpress

Mouse-specific skin and blood transcriptional responses after intradermal administration of flagellin

Project description:The study aimed at defining the local and systemic innate responses after intradermal injection of flagellin. For this purpose, mice were immunized by intradermal route with flagellin. Skin and blood were then sampled at selected times for microarray analyses. Mice were then immunized with the TLR5 agonist flagellin by intradermal route. Blood samples and punch biopsies of skin were sampled post-immunization and on mock animals. Total RNA was extracted and microarray experiments were performed as single-color hybridizations on Agilent 4x44K mouse whole genome catalog arrays (Agilent-014868) according supplier's recommendations.

2016-07-03 | E-GEOD-72016 | biostudies-arrayexpress

A Ferritin Mutant Induces Protective Immunity against Virulent Mycobacterium tuberculosis Infection

Project description:Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with ∆bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the ∆bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the ∆bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the ∆bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB.

2014-09-01 | GSE58810 | GEO

Prevention of Mycobacterium tuberculosis infection and disease in nonhuman primates following intravenous BCG vaccination

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.

2020-01-01 | GSE139598 | GEO

Vaccine inoculation route modulates early immunity and consequently antigen-specific immune response

Project description:Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.

2021-05-17 | E-MTAB-10309 | biostudies-arrayexpress

Intradermal but not intramuscular MVA immunizations protect against intravaginal tier2 SHIV challenges in macaques

Project description:Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 SHIV challenges in female macaques. Both routes of vaccination induced comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlated positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlated only with serum neutralizing activity. MVA-ID immunizations induced greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlated negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.

2023-07-27 | GSE219118 | GEO

Pig-specific skin transcriptional responses after intradermal administration of flagellin

Project description:The study aimed at defining the skin innate responses after intradermal injection of flagellin. For this purpose, pigs were immunized by intradermal route with flagellin and H1N1 antigen. Skin was then sampled for microarray analyses.

2016-01-31 | GSE72256 | GEO

Blood transcriptome following BCG vaccination administered via different routes in rhesus macaques

Project description:To determine the blood transcriptional response to BCG vaccination administered via different routes in rhesus macaques and identify correlates of vaccine-mediated protection against Mycobacterium tuberculosis (Mtb) challenge.

2023-06-19 | GSE218157 | GEO

Mouse-specific skin and blood transcriptional responses after intradermal administration of flagellin

2016-01-01 | GSE72016 | GEO

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