LEAPS therapeutic vaccines as antigen specific suppressors of inflammation in infectious and autoimmune diseases.
LEAPS therapeutic vaccines as antigen specific suppressors of inflammation in infectious and autoimmune diseases.
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DOI：
10.4172/2157-7560.1000149
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发表时间：
2012-09
期刊：
影响因子：
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通讯作者：
D. Zimmerman;Harold L Steiner;Roy Carmabula;E. Talor;K. Rosenthal
中科院分区：
文献类型：
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作者：
D. Zimmerman;Harold L Steiner;Roy Carmabula;E. Talor;K. Rosenthal
L.E.A.P.S.（™）（配体表位抗原呈递系统）技术平台已被用于开发针对传染病和自身免疫性疾病的免疫保护和免疫调节小肽疫苗。目前有几种产品处于不同的开发阶段，处于临床前阶段（在动物攻毒效力研究中）。疫苗肽能够引发动物对致命病毒（单纯疱疹病毒[HSV - 1]和甲型流感）感染的保护，或者能够阻断自身免疫性疾病的进展（例如在胶原蛋白诱导的关节炎[CIA]或实验性自身免疫性心肌炎[EAM]模型中的类风湿性关节炎）。L.E.A.P.S.技术是一种新型的T细胞免疫技术，能够设计和合成非重组的、专有的肽免疫原。将一种激活免疫系统的小肽与来自一种疾病相关蛋白的另一种小肽相结合，这样一种包含免疫细胞结合配体（ICBL）和一种疾病特异性表位的结合物，使得L.E.A.P.S.疫苗能够激活前体细胞分化并成为更成熟的细胞，从而引发和引导适当的T细胞反应。因此，可以针对不同疾病制备易于合成的、明确的免疫原，并且有可能像在小鼠中一样在人类中引发保护或治疗作用。L.E.A.P.S.疫苗有望用于治疗类风湿性关节炎和其他炎症性疾病以及感染，如流感和HSV1。其保护反应的特征是Th1免疫和免疫调节反应，表现为白细胞介素 - 12p70和干扰素 - γ（Th1细胞因子）增加，但炎症细胞因子肿瘤坏死因子 - α、白细胞介素 - 1和白细胞介素 - 17（Th2和Th17细胞因子）减少，以及抗体亚型的相应变化。LEAPS免疫原已直接在体内使用，或作为树突状细胞的体外激活剂，然后施用于宿主。
The L.E.A.P.S.(™) (Ligand Epitope Antigen Presentation System) technology platform has been used to develop immunoprotective and immunomodulating small peptide vaccines for infectious and autoimmune diseases. Several products are currently in various stages of development, at the pre-clinical stage (in animal challenge efficacy studies). Vaccine peptides can elicit protection of animals from lethal viral (herpes simplex virus [HSV-1] and influenza A) infection or can block the progression of autoimmune diseases (e.g. rheumatoid arthritis as in the collagen induced arthritis (CIA] or experimental autoimmune myocarditis (EAM) models). L.E.A.P.S. technology is a novel T-cell immunization technology that enables the design and synthesis of non-recombinant, proprietary peptide immunogens. Combination of a small peptide that activates the immune system with another small peptide from a disease-related protein, thus a conjugate containing both an Immune Cell Binding Ligand (ICBL) and a disease specific epitope, which allows the L.E.A.P.S. vaccines to activate precursors to differentiate and become more mature cells that can initiate and direct appropriate T cell responses. As such, readily synthesized, defined immunogens can be prepared to different diseases and are likely to elicit protection or therapy as applicable in humans as they are in mice. L.E.A.P.S. vaccines have promise for the treatment of rheumatoid arthritis and other inflammatory diseases and for infections, such as influenza and HSV1. The protective responses are characterized as Th1 immune and immunomodulatory responses with increased IL-12p70 and IFN-γ (Th1 cytokines) but reduced inflammatory cytokines TNF-α, IL-1 and IL-17 (Th2 and Th17 cytokines) and concomitant changes in antibody subtypes. LEAPS immunogens have been used directly in vivo or as ex vivo activators of DC which are then administered to the host.