IDENTIFYING EPITOPES THAT DEFINE SEROTYPES OF HIV1

描述：(改编自申请摘要)。许多微生物， 例如Strep。肺炎和脊髓灰质炎病毒被归类为 已被证明在疫苗开发中有用的血清型。类似地， 对HIV-1分离株进行血清型鉴定应有助于 开发一种针对HIV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，尤其是在包膜基因中。这有 导致对两个HIV-1基因组的鉴定，主要的(M)和 异常值(O)组。在M组中，已有10种基因型(A-J) 已确认身份。O组内的基因型别尚未确定。至 迄今为止，艾滋病毒的血清学分类没有遗传分类那么广泛 分类。免疫化学和中和试验与血清或 单抗、gp 120、gp4 1亚单位蛋白和病毒 已被用于研究HIV病毒的免疫学相关性。聚类 已对免疫化学和中和数据进行了分析 由独立的团体产生。这些分析的结果表明， HIV-1的血清型确实存在，并且它们与 遗传亚型。然而，到目前为止，单体、重组蛋白和 多肽，而不是病毒粒子上代表的天然包膜，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，使用血清而不是单抗。 申请者建议检查和开发免疫学基础，以期 使用以下方法对艾滋病毒进行分类：目标1，描述 通过鉴定不同HIV-1亚型完整病毒的抗原性 暴露在这些病毒表面和细胞上的表位 用抗gp20和抗gp41单抗感染这些病毒。目标2， 为了定义在免疫上相关的病毒簇(血清型)， 以确定这些血清型的共同表位，并鉴定 可用于HIV-1分离株的血清学分型。

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.