IDENTIFYING EPITOPES THAT DEFINE SEROTYPES OF HIV1
IDENTIFYING EPITOPES THAT DEFINE SEROTYPES OF HIV1
批准号:
2751251
负责人:
Phillipe N Nyambi
金额:
$24.75万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-09-30 至 2000-09-29
关键词:
AIDS vaccines HIV envelope protein gp120 HIV envelope protein gp41 antibody neutralization test cell mediated cytotoxicity cross immunity enzyme linked immunosorbent assay flow cytometry human immunodeficiency virus 1 human tissue microorganism classification monoclonal antibody serotyping vaccine development virion virus antigen
中文摘要
描述:(改编自应用摘要)。 许多微生物,
例如链球菌。 肺炎和脊髓灰质炎病毒,已被归类为
已被证明可用于疫苗开发的血清型。 类似地,
将HIV-1分离株鉴定为血清型应有助于
开发一种抗HIV 1的多价疫苗。 到目前为止,
人类免疫缺陷病毒(HIV)的分类是基于其
广泛的遗传变异,特别是在包膜基因。 这
导致两个基因型HIV- 1组的鉴定,主要(M)和
离群值(O)组。 在M组中,10种基因型(A-J)已被发现。
鉴定 O组内的基因型尚未确定。 到
迄今为止,艾滋病毒的血清学分类不如遗传学分类广泛,
分类. 免疫化学和血清中和试验,或
单克隆抗体(mAbs)和gp 120、gp 4 1亚单位蛋白以及病毒
已被用于研究HIV病毒的免疫相关性。 集群
对免疫化学和中和数据进行了分析,
由独立的团体组成。 这些分析的结果表明,
HIV-1的血清型确实存在,它们与
基因亚型 然而,到目前为止,单体,重组蛋白和
肽,而不是病毒体上的天然包膜,已经被
用于免疫化学分析。 此外,对于中和数据,
对其进行聚类分析,使用血清而不是mAb。
申请人建议检查和开发免疫学基础,
使用以下方法对HIV进行分类:AIM 1,描述
通过鉴定不同HIV-1进化枝的完整病毒的抗原图谱,
暴露在这些病毒表面和细胞上的表位
感染这些病毒,通过使用抗gp 120和抗gp 41单克隆抗体。 AIM 2,
为了定义免疫学上相关的病毒簇(血清型),
确定这些血清型共有的表位,并鉴定
可用于HIV 1分离株的血清分型。
英文摘要
DESCRIPTION: (Adapted from application abstract). Many microorganisms,
such as Strep. pneumonia and Polio virus, have been classified into
serotypes which have proven useful in vaccine development. Similarly, the
characterization of HIV-1 isolates into serotypes should be useful in the
development of a polyvalent vaccine against HIV 1. Until now,
classification of human immunodeficiency virus (HIV) has been based on its
extensive genetic variability, especially in the envelope gene. This has
lead to the identification of two genotypic HIV- 1 groups, the major (M) and
the outlier (O) groups. Within the M group, 10 genotypes (A-J) have been
identified. Genotypes within the O group are yet to be identified. To
date, serological classification of HIV has been less extensive than genetic
classification. Immunochemical and neutralization assays with sera or
monoclonal antibodies (mAbs) and gp 120, gp4 1 subunit proteins, and viruses
have been used to study the immunologic relatedness of HIV viruses. Cluster
analyses have been applied to the immunochemical and neutralization data
generated by independent groups. The results of these analyses suggest that
serotypes of HIV-1 do indeed exist and that they do not correlate with
genetic subtypes. However, until now, monomeric, recombinant proteins and
peptides, rather than the native envelopes represented on virions, have been
used for immunochemical analysis. Furthermore, for the neutralization data
on which cluster analysis was performed, sera rather than mAbs were used.
The applicants propose to examine and develop an immunologic basis for
classifying HIV using the following approaches: AIM 1, to describe the
antigenic landscape of intact viruses of diverse HIV-1 clades by identifying
epitopes that are exposed on the surface of these viruses, and on cells
infected with these viruses, by using anti-gpl20 and anti-gp41 mAbs. AIM 2,
to define clusters of viruses that are related immunologically (serotypes),
to define the epitopes common to these serotypes, and to identify mAbs that
can be used in serotyping HIV 1 isolates.
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会议论文
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