Group M-based HIV-1 Gag peptides are frequently targeted by T cells in chronically infected US and Zambian patients

Group M-based HIV-1 Gag peptides are frequently targeted by T cells in chronically infected US and Zambian patients
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DOI:
10.1097/01.aids.0000206501.16783.67
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发表时间:
2006-02-14
期刊:
影响因子:
3.8
通讯作者:
Goepfert, PA
Goepfert, PA
中科院分区:
医学2区
文献类型:
--
作者:
Bansal, A;Gough, E;Goepfert, PA

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背景:HIV-1的巨大序列多样性一直是开发全球有用的艾滋病疫苗的主要障碍。共识和基于祖先序列的免疫原最大限度地减少了当代分离株和疫苗株之间的遗传距离。因此,这些序列可能是HIV疫苗的候选序列或作为评估Gag特异性应答的通用试剂集。方法:在本研究中,我们测定了来自两个参考人群的HIV-1感染者的T细胞对共识(A、B、C和M亚型)、祖先(M和B亚型)和HXB2 Gag多肽(15-MERS重叠11)的反应性。我们用干扰素-γ-酶联免疫吸附斑点试验评估了43例慢性感染的美国人(B亚型)和13名赞比亚人(C亚型)的GAG特异性T细胞反应。结果:在所有被评估的7种GAG免疫原中,我们的发现显示出广泛的交叉反应,近70%。在B亚型感染的美国患者中,共识M序列引起的反应水平与共识B、祖先B亚型和HXB2多肽相似。在感染C亚型的赞比亚受试者中,共识C、共识M和祖传M多肽都能引起相似广度和幅度的反应。结论:我们的数据表明,基于共识或祖传M序列的肽库可以用来评估B亚型或C亚型免疫原诱导的GAG特异性反应。(C)2006年,Lippincott Williams&Wilkins。
Background: The enormous sequence diversity of HIV-1 has been a major obstacle in the development of a globally useful vaccine for AIDS. The consensus and ancestral sequence-based immunogens minimize the genetic distance between contemporary isolates and vaccine strains. Hence these sequences may be promising candidates for HIV vaccines or serve as a universal reagent set for evaluating Gag-specific responses.Methods: In this study, we measured the T-cell reactivity to consensus (subtype A, B, C and group M), ancestral (group M and subtype B) and HXB2 Gag peptides (15-mers overlapping by 11) in HIV-1-infected subjects from two reference populations. We evaluated the Gag-specific T-cell responses in 43 chronically infected US (subtype B) and 13 Zambian (subtype C) subjects using an interferon-gamma enzyme-linked immunosorbent spot assay.Results: Our findings demonstrate abroad cross-reactivity of nearly 70% among all the seven Gag immunogens evaluated. Consensus M sequences elicited similar levels of responses as did the consensus B, ancestral subtype B and HXB2 peptides in subtype B-infected US patients. In subtype C-infected Zambian subjects, responses of similar breadth and magnitude were elicited by consensus C, consensus M and ancestral M peptides.Conclusion: Our data demonstrate that peptide pools based on consensus or ancestral M-based sequences can be used to evaluate Gag-specific responses elicited by subtype B or subtype C-based immunogens. (C) 2006 Lippincott Williams & Wilkins.