Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation

Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation
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DOI:
10.1016/j.vaccine.2006.06.009
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发表时间:
2006-11-17
期刊:
影响因子:
5.5
通讯作者:
Self, Steven G.
Self, Steven G.
中科院分区:
医学3区
文献类型:
--
作者:
Li, Fusheng;Malhotra, Uma;Self, Steven G.

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数十种人类免疫缺陷病毒1型(HIV-1)候选疫苗专门设计用于引发细胞毒性t淋巴细胞(CTL)反应,已经进入临床试验的管道。面对流行毒株广泛的病毒遗传多样性,评估这些HIV-1候选疫苗的免疫原性和潜在疗效具有挑战性。需要标准化的肽试剂来确定t细胞反应的幅度和潜在广度,特别是对HIV-1循环毒株的反应。为此,我们开发了一种基于t细胞识别模式的生物识别方法,用于定义标准化试剂。评估了Los Alamos数据库中的循环菌株,并生成了定义所有潜在t细胞表位(pte)的标准化算法。虽然可以鉴定出许多独特的pte,但基于数据库中流行菌株的有限数量,我们将其定义为疫苗重要pte (vip),用于选择通用的标准化HIV-1肽组进行基于ctl的疫苗评估。PTE肽集的可用性通过检测HIV-1亚型B感染的nef特异性CTL反应得到证明。(c) 2006 Elsevier Ltd.版权所有。
Dozens of human immunodeficiency virus-type 1 (HIV-1) vaccine candidates specifically designed to elicit cytotoxic T-lymphocyte (CTL) responses have entered the pipeline of clinical trials. Evaluating the immunogenicity and potential efficacy of these HIV-1 vaccine candidates is challenging in the face of the extensive viral genetic diversity of circulating strains. Standardized peptide reagents to define the magnitude and potential breadth of the T-cell response, especially to circulating strains of HIV-1, are needed. For this purpose we developed a biometric approach based on T-cell recognition pattern for defining standardized reagents. Circulating strains in the Los Alamos database were evaluated and standardized algorithms to define all potential T-cell epitopes (PTEs) were generated. While many unique PTEs could be identified, a finite number based upon prevalence of circulating strains in the database, which we define as vaccine-important PTEs (VIPs), were used to select a common standardized panel of HIV-1 peptides for CTL-based vaccine evaluation. The usability of PTE peptide set was manifested by detection of Nef-specific CTL responses in HIV-1 subtype B infections. (c) 2006 Elsevier Ltd. All rights reserved.