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Priming characteristics of peptide mimotopes of carbohydrate antigens

机译:糖类抗原肽模拟物的启动特性

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Immunization with peptide mimetics of carbohydrate antigens can induce functional carbohydrate-reactive antibodies. Here, we examine the immune characteristics of alternative approaches in prime and boost strategies using glycosylated HIV-1 envelope protein and model tumor associated carbohydrate antigens. Our results indicate that peptide mimotopes either in a DNA or carrier-conjugated for-mat can induce comparable levels of IgM and IgG. Carbohydrate boosting of peptide-primed animals does not affect end-point titer, however, boosting mediates a stable long lasting carbohydrate reactive IgM response, not achievable by carbohydrate immunization alone. Boosting with carbohydrate in animals primed with DNA- or peptide-conjugate, facilitates the induction of detectable IgG with a dominant IgG2a isotype. Immunization with HIV-1 envelope glycoprotein of peptide-primed animals induces different IgG isotype profiles with a dominant IgG I antibody. We observed that HIV-1 envelope glycoprotein immunization of peptide primed mice induces a cross-reactive cellular response, as detected by cytokine secretion, which lends to IFN-gamma production upon splenocyte stimulation and CTL activity against recombinant vaccinia virus infected cells after in vitro stimulation. DNA immunization with mimotope, inclusion of a T-cell epitope from the HIV-1 envelope protein in the expression cassette and co-administration with IL-12 or GM-CSF encoding plasmids activate a cellular response to the HIV-1 envelope protein.
机译:用碳水化合物抗原的肽模拟物进行免疫可以诱导功能性碳水化合物反应性抗体。在这里,我们检查了使用糖基化的HIV-1包膜蛋白并模拟肿瘤相关碳水化合物抗原的初免和加强策略中替代方法的免疫特性。我们的结果表明,DNA或与载体偶联的for-mat中的肽模拟物可以诱导相当水平的IgM和IgG。肽致敏动物的碳水化合物增强作用不会影响终点滴度,但是,增强作用可介导稳定的持久性碳水化合物反应性IgM反应,这是单独通过碳水化合物免疫无法实现的。在以DNA-或肽-共轭物引发的动物体内以碳水化合物加强免疫,可促进具有显性IgG2a同型的可检测IgG的诱导。用肽引发的动物的HIV-1包膜糖蛋白免疫可诱导显性IgG I抗体产生不同的IgG同种型。我们观察到,肽引发的小鼠的HIV-1包膜糖蛋白免疫诱导了交叉反应性细胞应答,如通过细胞因子分泌所检测到的,该因子在脾细胞刺激后可产生IFN-γ,在体外刺激后对重组牛痘病毒感染的细胞具有CTL活性。用模拟表位进行DNA免疫,在表达盒中包含来自HIV-1包膜蛋白的T细胞表位,并与IL-12或GM-CSF编码质粒共同给药激活了对HIV-1包膜蛋白的细胞应答。

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