Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope
Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope
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DOI：
10.1128/jvi.00184-09
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发表时间：
2009-05-15
影响因子：
5.4
通讯作者：
Arnold, Eddy
中科院分区：
文献类型：
--
作者：
Arnold, Gail Ferstandig;Velasco, Paola K.;Arnold, Eddy
在开发艾滋病疫苗成分的努力中，我们构建了重组人鼻病毒的组合文库，这些病毒展示了人类免疫缺陷病毒1型（HIV - 1）gp41近膜外区高度保守的ELDKWA表位。我们使用广泛中和的人单克隆抗体2F5来筛选其ELDKWA构象与HIV相似的病毒。用不同的嵌合体对豚鼠进行免疫，其中一些用基于ELDKWA的肽进行加强免疫，诱导出能够中和多种亚型和共受体使用情况的HIV - 1假病毒的抗体。这些重组免疫原是首次报道的使用基于ELDKWA的表位引发对HIV - 1广泛（尽管适度）中和的免疫原，也是少数报道的针对任何重组HIV表位引发广泛中和的免疫原之一，为开发有效的艾滋病疫苗成分提供了关键的进展。
In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.