Li Fusheng, Malhotra Uma, Gilbert Peter B, Hawkins Natalie R, Duerr Ann C, McElrath Juliana M, Corey Lawrence, Self Steven G
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Vaccine. 2006 Nov 17;24(47-48):6893-904. doi: 10.1016/j.vaccine.2006.06.009. Epub 2006 Jun 27.
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.
数十种专门设计用于引发细胞毒性T淋巴细胞（CTL）反应的1型人类免疫缺陷病毒（HIV-1）疫苗候选物已进入临床试验阶段。面对循环毒株广泛的病毒基因多样性，评估这些HIV-1疫苗候选物的免疫原性和潜在效力具有挑战性。需要标准化的肽试剂来确定T细胞反应的强度和潜在广度，尤其是针对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统计学方法来定义标准化试剂。对洛斯阿拉莫斯数据库中的循环毒株进行了评估，并生成了定义所有潜在T细胞表位（PTE）的标准化算法。虽然可以识别出许多独特的PTE，但基于数据库中循环毒株的流行率确定了有限数量的PTE，我们将其定义为疫苗重要PTE（VIP），用于选择一组用于基于CTL的疫苗评估的通用标准化HIV-1肽。PTE肽组的可用性通过在HIV-1 B亚型感染中检测Nef特异性CTL反应得到体现。
