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Antigen-specific Immune Responses (antigen-specific + immune_response)

Distribution by Scientific Domains

Life Sciences	33%

Selected Abstracts

NSOM- and AFM-based nanotechnology elucidates nano-structural and atomic-force features of a Y. pestis V immunogen-containing particle vaccine capable of eliciting robust response

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2009
Gucheng Zeng
Abstract It is postulated that unique nanoscale proteomic features of immunogen on vaccine particles may determine immunogen-packing density, stability, specificity, and pH-sensitivity on the vaccine particle surface and thus impact the vaccine-elicited immune responses. To test this presumption, we employed near-filed scanning optical microscopy (NSOM)- and atomic force microscopy (AFM)-based nanotechnology to study nano-structural and single-molecule force bases of Yersinia pestis (Y. pestis) V immunogen fused with protein anchor (V-PA) loaded on gram positive enhancer matrix (GEM) vaccine particles. Surprisingly, the single-molecule sensitive NSOM revealed that ,90% of V-PA immunogen molecules were packed as high-density nanoclusters on GEM particle. AFM-based single-molecule force analyses indicated a highly stable and specific binding between V-PA and GEM at the physiological pH. In contrast, this specific binding was mostly abrogated at the acidic pH equivalent to the biochemical pH in phagolysosomes of antigen-presenting-cells in which immunogen protein is processed for antigen presentation. Intranasal mucosal vaccination of mice with such immunogen loaded on vaccine particles elicited robust antigen-specific immune response. This study indicated that high-density, high-stability, specific, and immunological pH-responsive loading of immunogen nanoclusters on vaccine particles could readily be presented to the immune system for induction of strong antigen-specific immune responses. [source]

Peripheral tolerance limits CNS accumulation of CD8 T cells specific for an antigen shared by tumor cells and normal astrocytes

GLIA, Issue 15 2008
Thomas Calzascia
Abstract T cell mediated immunotherapies are proposed for many cancers including malignant astrocytoma. As such therapies become more potent, but not necessarily more tumor-specific, the risk of collateral autoimmune damage to normal tissue increases. Tumors of the brain present significant challenges in this respect, as autoimmune destruction of brain tissue could have severe consequences. To investigate local immune reactivity toward a tumor-associated antigen in the brain, transgenic mice were generated that express a defined antigen (CW3170,179) in astroglial cells. The resulting six transgenic mouse lines expressed the transgenic self-antigen in cells of the gastrointestinal tract and CNS compartments, or in the CNS alone. By challenging transgenic mice with tumor cells that express CW3, self/tumor-specific immune responses were visualized within a normal polyclonal T cell repertoire. A large expansion of the endogenous CW3170,179 -specific CD8 T cell population was observed in nontransgenic mice after both subcutaneous and intracerebral implantation of tumor cells. In contrast, CW3170,179 -specific immune responses were not observed in transgenic mice that exhibited extracerebral transgene expression. Importantly, in certain groups of mice in which transgene expression was restricted to the CNS, antigen-specific immune responses occurred when tumor was implanted subcutaneously, but not intracerebrally. This local immune tolerance in the brain was induced via peripheral (extrathymic) rather than central (thymic) tolerance mechanisms. Thus, this study highlights the role of regional immune regulation in the prevention of autoimmunity in the brain, and the potential impact of these mechanisms for brain tumor immunotherapy. © 2008 Wiley-Liss, Inc. [source]

NSOM- and AFM-based nanotechnology elucidates nano-structural and atomic-force features of a Y. pestis V immunogen-containing particle vaccine capable of eliciting robust response

Early events of electroporation-mediated intramuscular DNA vaccination potentiate Th1-directed immune responses

THE JOURNAL OF GENE MEDICINE, Issue 9 2005
Eirik Grønevik
Abstract Background Application of electrical pulses after DNA injection into muscle increases expression of the encoded genes, and is shown to improve antigen-specific immune responses when used for DNA vaccination. In addition, electroporation causes tissue injury and inflammatory reactions. Together with immune stimulatory motifs in the injected DNA these factors may potentiate the immune response by acting as adjuvants for the antigen. Here, we have examined the role of these factors in promoting the efficiency of DNA vaccination. Methods We injected a plasmid DNA vector containing the gene Ag85B from M. tuberculosis into mouse quadriceps muscles followed by electroporation. Ag85B was under control of a Tet-responsive promoter, and was expressed either immediately or up to 28 days later by administrating doxycycline to the mice. Delayed expression was combined with injection of non-coding DNA or saline with or without electroporation to examine the ability of these factors to enhance the Ag85B-specific antibody response in the blood and cellular responses in the spleen. Blood samples were analysed with ELISA, while the number of Ag85B-specific IFN-,- and IL-4-producing spleenocytes was analysed with ELISpot. Results Delaying Ag85B expression by 5 or 28 days caused lower anti-Ag85B-specific IgG2a levels. In contrast, the IgG1 antibody response was not significantly affected. Injection of non-coding DNA followed by electroporation moderately increased the IgG2a response. Delaying the Ag85B expression by 28 days reduced the average number of Ag85B-specific IFN-,-producing spleenocytes by over 60%. No significant change in the number of IL-4-producing Ag85B-specific spleenocytes was observed. Conclusions These results suggest that DNA and electroporation per se may act as good adjuvants in promoting efficient Th1-directed responses during DNA vaccination. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Conditioning in 2 × 2 Tables

BIOMETRICS, Issue 1 2009
Michael A. Proschan
Summary Two-by-two tables arise in a number of diverse settings in biomedical research, including analysis of data from a clinical trial with a binary outcome and gating methods in flow cytometry to separate antigen-specific immune responses from general immune responses. These applications offer interesting challenges concerning what we should really be conditioning on,the total number of events, the number of events in the control condition, etc. We give several biostatistics examples to illustrate the complexities of analyzing what appear to be simple data. [source]

Generation of mature dendritic cells fully capable of T helper type 1 polarization using OK-432 combined with prostaglandin E2

CANCER SCIENCE, Issue 12 2003
Marimo Sato
Dendritic cell (DC) administration appears to be a very promising approach for the immunotherapy of cancer. The results of clinical studies have suggested that the nature and the magnitude of antitumor immune responses are critically affected by DC functions, including production of T helper type 1 (Th1)-inducing cytokines, activation of T cell subsets and natural killer (NK) cells, and migration from peripheral tissues to the T cell area of the draining lymph nodes. Administration of immature DCs could fail to fully stimulate antigen-specific immune responses and might induce tolerance under some conditions. In this study, we developed a method to obtain fully mature DCs, and we compared in detail the DCs thus obtained with those obtained using a maturation stimulus termed monocyte-derived medium (MCM)-mimic, which is a mixture of recombinant cytokines and prostaglandin E2 (PGE2) mimicking the components of monocyte-conditioned medium. Using DCs derived from monocytes of advanced cancer patients in this study, we found that DCs stimulated with OK-432 alone showed phenotypes similar to those of mature DCs induced using MCM-mimic, though with better secretion of IL-6 and IL-12. However, these DCs were found to have poor migratory capacity associated with the marginal expression of CCR7. When OK-432 was combined with PGE2, the CCR7 expression and migratory capacity of DCs were significantly improved without impairing other immuno-stimulatory functions. These results suggest that stimulation with the combination of OK-432 and PGE2 could be applicable as an alternative to MCM-mimic in clinical trials which require fully matured DCs to induce Th1-type immune responses against tumor cells even in patients with advanced cancer. [source]