Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults.
Project description:We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin. Interpretation: The unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation.
Project description:Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi. Dogs are at high risk of exposure to ticks and tick-borne pathogens, including B. burgdorferi. Immunodiagnostic assays are usually based on whole-cell preparations of B. burgdorferi as substrate and, consequently, interpretation of results is confounded by antibody cross-reactivity between borrelial antigens and other bacterial species, as well as the anti-LB vaccination status of the dog. For this study, we examined sera from 33 dogs that were experimentally infected with B. burgdorferi through tick bite. These sera were compared with sera from uninfected dogs in their reactivities to 72 different recombinant B. burgdorferi antigens and 24 OspC protein types on a protein microarray. Amongst antigens frequently recognized by infected dogs were several known to be immunogens for humans, such as Decorin-binding protein A (BBA25), BBA64, fibronectin-binding protein (BBK32), VlsE, Erp and Bdr, CRASP proteins, OspC proteins and some flagellar antigens. Of special interest were the novel antigens BBB14 and BB0844, both hypothetical lipoproteins about which very little is currently known, and that were frequently and strongly recognized by infected dog sera. The antibody response of B. burgdorferi-infected dogs presents both similarities and differences from human counterparts, and both can be important for improvement of canine LB diagnosis and vaccine development. Antibody profiling was performed on sera from dogs experimentally-infected with B. burgdorferi and unexposed controls against antigens of B. burgdorferi. Thirty-three serum samples from experimental infections, and 5 unexposed controls were probed on a protein microarray displaying 24 OspC proteins of B. burgdorferi .
Project description:Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi. Dogs are at high risk of exposure to ticks and tick-borne pathogens, including B. burgdorferi. Immunodiagnostic assays are usually based on whole-cell preparations of B. burgdorferi as substrate and, consequently, interpretation of results is confounded by antibody cross-reactivity between borrelial antigens and other bacterial species, as well as the anti-LB vaccination status of the dog. For this study, we examined sera from 33 dogs that were experimentally infected with B. burgdorferi through tick bite. These sera were compared with sera from uninfected dogs in their reactivities to 72 different recombinant B. burgdorferi polypeptides on a protein microarray. Amongst antigens frequently recognized by infected dogs were several known to be immunogens for humans, such as Decorin-binding protein A (BBA25), BBA64, fibronectin-binding protein (BBK32), VlsE, Erp and Bdr, CRASP proteins, OspC proteins and some flagellar antigens. Of special interest were the novel antigens BBB14 and BB0844, both hypothetical lipoproteins about which very little is currently known, and that were frequently and strongly recognized by infected dog sera. The antibody response of B. burgdorferi-infected dogs presents both similarities and differences from human counterparts, and both can be important for improvement of canine LB diagnosis and vaccine development. Antibody profiling was performed on sera from dogs experimentally-infected with B. burgdorferi and unexposed controls against antigens of B. burgdorferi. Thirty-three serum samples from experimental infections, and 6 unexposed controls were probed on a protein microarray displaying 72 unique proteins of B. burgdorferi .
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the OMV component of 4CMenB vaccine in infant sera before and after vaccination
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the OMV component of 4CMenB vaccine in mouse sera before and after immunization.
Project description:Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20-30%. T cell checkpoint blockade immunotherapies have revolutionized cancer treatment in the last decade, but their impact remains limited in osteosarcoma. In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterization of a unique sample set comprising multiple osteosarcoma samples from seven patients, collected throughout the progression of the disease. We performed RNA-sequencing and imaging mass cytometry analysis on those samples to reveal the immunological landscape during osteosarcoma progression. Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anti-cancer immunity were enriched in metastatic lesions as compared to primary tumors. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly MAGEA-related antigens, in osteosarcoma metastases. Their overexpression in metastatic lesions was confirmed at protein level and positive expression of MAGEA3 in primary tumors showed a significant association with metastasis free survival. Importantly, we demonstrated the presentation of MAGE-derived peptides in three osteosarcoma cell lines. These findings indicate a concurrent augmentation of cytotoxic anti-tumor immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation warrants the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.
Project description:Autoimmune regulator (Aire) is a unique transcriptional regulator that induces promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for induction of immunological self-tolerance. Although several recent studies provided very important molecular insights into how Aire operates, a more comprehensive understanding of this process still remains elusive. Here we demonstrate that a lysine deacetylase Sirtuin-1 (Sirt1) is predominantly expressed in mature Aire+ mTECs, where it is required for expression of Aire-dependent TRA genes and a subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and uncovers a unique functional role for Sirt1 in preventing organ-specific autoimmunity. ~100ng of total RNA isolated by Trizol extraction from MHC-II low and high mTECs (pool of 3 mice) was used to generate poly-A-selected transcriptome libraries using the non-directionnal TruSeq V3 RNA Sample Prep Kit (without additional pre-amplification) following the manufacturer's protocols. Enrichment of DNA fragment with adapter molecules on both ends was done using 15 cycles of PCR amplification using the Illumina PCR mix and primer cocktail. Paired-end (2 × 100 bp) sequencing was performed using the Illumina HiSeq2000 machine.