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Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

ABSTRACT: Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer cells, T cells, and B cells after administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 post-vaccination, several antigen presentation-related pathways, including MHC class I-mediated antigen processing and presentation, were enriched in monocytes and neutrophils and expression of HLA class I proteins was increased in the Adjuvant System 03 group. We identified several protein families whose proteomic responses predicted seroprotective antibody responses (>1:40 hemagglutination inhibition titer), including inflammation and oxidative stress proteins at day 1 as well as immunoproteasome subunit (PSME1 and PSME2) and HLA class I proteins at day 3 in monocytes. While comparison between temporal proteomic and transcriptomic results showed little overlap overall, enrichment of the MHC class I antigen processing and presentation pathway in monocytes and neutrophils was confirmed by both approaches.

SUBMITTER: Galassie AC

PROVIDER: S-EPMC5736144 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

Galassie Allison C AC Goll Johannes B JB Samir Parimal P Jensen Travis L TL Hoek Kristen L KL Howard Leigh M LM Allos Tara M TM Niu Xinnan X Gordy Laura E LE Creech C Buddy CB Hill Heather H Joyce Sebastian S Edwards Kathryn M KM Link Andrew J AJ

Proteomics 20170601 12

Adjuvants enhance immunity elicited by vaccines through mechanisms that are poorly understood. Using a systems biology approach, we investigated temporal protein expression changes in five primary human immune cell populations: neutrophils, monocytes, natural killer cells, T cells, and B cells after administration of either an Adjuvant System 03 adjuvanted or unadjuvanted split-virus H5N1 influenza vaccine. Monocytes demonstrated the strongest differential signal between vaccine groups. On day 3 ...[more]

PMID: 28508465

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Project description:BackgroundA goal of cancer vaccines is to induce strong T cell responses to tumor antigens, but the delivery method, schedule, and formulation of cancer vaccines have not yet been optimized. Adjuvants serve to increase the immune response against vaccine antigens. However, little is known about the impact of adjuvants plus antigen and their delivery schedule on the immunologic milieu in the vaccine-site microenvironment (VSME). We hypothesized that antigen processing and presentation may occur directly in the VSME, that adding the toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) would enhance markers of immune activation, and that the immune signatures would be enhanced further by repeated vaccination in the same skin site rather than after multiple vaccines in different skin locations.MethodsUsing RNA sequencing, we evaluated VSME biopsies from patients undergoing subcutaneous/intradermal peptide vaccination against melanoma, with incomplete Freund's adjuvant (IFA) with or without pICLC. Differential gene expression analyses and gene set enrichment analyses were performed using R. False discovery rate corrected p values <0.05 were considered significant.ResultsWe found that addition of peptide antigens to IFA enhanced antigen presentation pathways and a tertiary lymphoid structure gene-signature locally at the VSME. Addition of pICLC to IFA + peptide induced an immunologically favorable VSME 1 week after injection but had little impact on the VSME after three injections, compared with IFA + peptide alone. Repeated same-site injection of IFA + peptide antigens induced a VSME with more dendritic cell activation, Th1 dominance, and TLR adaptor protein gene expression than that induced by injections at different, rotating skin locations.ConclusionsThese data suggest that the vaccine-site itself may be a critically important location contributing to vaccine immunity rather than just the draining lymph node, that IFA induces a favorable VSME with TLR agonist being most beneficial early in the vaccine course, and that same-site injections lead to persistent stimulation of immune pathways that may be beneficial in eliciting antigen specific T cell expansion.

Project description:Penile squamous cell carcinoma (PSCC) is a largely neglected condition, predominantly affecting underdeveloped regions, and is associated with risk factors such as low socioeconomic status, phimosis, and human papillomavirus (HPV) infection. Unlike other urogenital cancers, its pathophysiology and therapeutic targets remain poorly understood, particularly regarding the immune response to the tumor microenvironment. This study aims to investigate immune cell infiltration profiles, dendritic cell maturation, and lymphocyte apoptosis in both HPV-positive and HPV-negative PSCC. Clinical and histopathological data, along with peripheral blood and tumor tissue samples, were collected from 30 patients (66.6% were HPV-positive and 33.3% HPV-negative), with an additional 19 healthy donors serving as controls. Tumor-infiltrating immune cells were analyzed following enzymatic digestion of tumor tissue, enabling detailed phenotypic characterization. A simulated tumor microenvironment was created using supernatants derived from primary cultures of HPV-positive PSCC tumors. Peripheral blood mononuclear cells were isolated and differentiated into dendritic cells (Mo-DCs) for further phenotyping and lymphoproliferation assays. Lymphocytes from healthy donors and patients were exposed to tumor culture supernatants to evaluate apoptosis induced by the tumor microenvironment. Results showed that HPV-positive tumors exhibited lower T lymphocyte frequencies compared to HPV-negative tumors. Additionally, patients infected with high-risk HPV demonstrated reduced maturation rates of Mo-DCs and decreased expression of co-stimulatory molecules on these cells compared to healthy donors. Furthermore, Mo-DCs from hrHPV-positive patients showed impaired lymphoproliferation capacity relative to controls, while HPV-negative patients exhibited a trend towards reduced lymphoproliferative ability. Regarding the simulated tumor microenvironment, lymphocytes from healthy donors underwent apoptosis, contrasting with patients' lymphocytes, which showed increased viability when cultured with tumor supernatants. These results underscore the impact of HPV infection on T lymphocyte infiltration, Mo-DC maturation, and lymphocyte survival in PSCC, offering critical insights for advancing our understanding of the tumor microenvironment and guiding the development of immunotherapy strategies.

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Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

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Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination.

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