M M Szachniewicz, K E van Meijgaarden, E Kavrik, W Jiskoot, J A Bouwstra, M C Haks, A Geluk, T H M Ottenhoff
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引用次数: 0
Abstract
Tuberculosis (TB) is a major global health problem, and the development of effective and safe vaccines is urgently needed. CD8+ T-cells play an important role alongside CD4+ T-cells in the protective immune response against TB. pH-sensitive liposomes are hypothesized to boost CD8+ T-cell responses by promoting class I presentation through a mechanism involving pH-dependent endosomal escape and the cytosolic transfer of antigens. The aim of the study was to explore the potential of pH-sensitive liposomes as a novel delivery system for a multi-stage protein subunit vaccine against TB in primary human cells. The liposomes were formulated with the fusion antigen Ag85b-ESAT6-Rv2034 (AER), which was previously shown to be effective in reducing bacterial load in the lungs HLA-DR3 transgenic mice and guinea pigs. The liposomes were assessed in vitro for cellular uptake, cell viability, upregulation of cell surface activation markers, induction of cytokine production using human monocyte-derived dendritic cells (MDDCs), and activation of human antigen-specific T-cells. Liposome DOPC:DOPE:DOBAQ:EPC (3:5:2:4 M ratio) was effectively taken up, induced several cell surface activation markers, and production of CCl3, CCL4, and TNFα in MDDCs. It also induced upregulation of CD154 and IFNγ in T-cell clones in an antigen-specific manner. Thus, cationic pH-sensitive liposome-based TB vaccines have been demonstrated to be capable of inducing robust protective Mtb-specific immune responses, positioning them as promising candidates for effectiveTBvaccination.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.