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原文:
title:
Development of replication-defective lymphocytic choriomeningitis
virus vectors for the induction of potent CD8+ T cell immunity
Abstract:
Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8+ T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.
中文:
题目:旨在诱导潜在CD8+T细胞免疫的,复制缺陷的淋巴细胞性脉络丛脑膜炎病毒载体技术进步
摘要:淋巴细胞性脉络丛脑膜炎病毒(LCMV)表现出对树突状细胞的自然向性以及感染源性,这些所表现出来的特征诱导保护性的CD8+细胞免疫(细胞毒性T淋巴细胞(CTL))。这里我们已经将这个沙粒病毒的免疫生物学用于疫苗呈递。
通过使用生产细胞组织性合成病毒糖蛋白(GP),用疫苗的抗原替换基因编码LCMV糖蛋白从而产生复制缺陷疫苗载体。这些rLCMV疫苗诱发的CTL应答,以重要的、细胞因子的方面,等效于或更甚于由重组的腺病毒5或重组疫苗性病毒的应答,而且前者在一些模型中表现出更加有效地保护。与重组腺病毒5相反,rLCMV不能诱导特定载体抗体免疫,这种免疫方便了为加强种疫苗的同一种载体再次给药。此外,rLCMV诱导T辅助性1CD4+T细胞应答和保护性的中和疫苗抗原的抗体。这些特征,加之人类的低血清阳性率,表明rLCMV可能表现出作为对抗感染性疾病和癌症的疫苗平台的实用性。
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