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Identification of HTLV-1 neutralizing epitopes and the development of an HTLV-1 peptide based vaccine

HTLV-1 中和表位的鉴定以及基于 HTLV-1 肽的疫苗的开发

基本信息

批准号：
04670391
负责人：
NAKAMURA Minoru
金额：
$ 1.34万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670391/
关键词：
B lymphocyte repertoire human monoclonal antibody anti-HTLV-1 antibody neutralizing epitope peptide based vaccine B cell epitope T cell epitope anti-mitochondrial antibody 抗HTLV-1 抗体 B Cell エピトープ T Cell エピトープ抗HTLV-I抗体 B cell エピトープ

项目摘要

We have generated a number of human monoclonal antibodies(mAb) to HTLV-1 by transforming B lymphocyte with EBV.Peripheral blood obtained from patients with HAM/TSP was used as a source of B lymphocytes committed to the production of IgG antibodies to HTLV-1. By using these mAb, we have identified the principle linear neutralizing B cell epitopes of HTLV-1 on the envelope protein gp46 a.a.187-199. Thus, we proposed that this region would be a good candidate for a peptide based HTLV-1 vaccine. In order to develop a peptide based vaccine which can induce a high titer of neutralizing antibodies against HTLV-1, we first synthesized peptides of various lengths containing an a.a.sequence of the principle neutralizing determinant of HTLV-1 gp46 a.a.187-199. Then, we conjugated these peptides with MAP.High titers of neutralizing antibodies were induced by immunization of MAP181-210 in various strains of rats and rabbits. We also identified the major T cell epitope on gp46 a.a.194-210 in various strains of rats Furthermore, MAP181-210 contains a T cell helper epitope on a.a.194-210 in humans with various HLA haplotypes. It is therefore possible that MAP181-210 could become one of the first candidates of a peptide based vaccine for human use.

我们用EB病毒转化B淋巴细胞，制备了一系列抗HTLV-1的人源性单克隆抗体（mAb）。从HAM/TSP患者的外周血中获得的B淋巴细胞被用作产生抗HTLV-1 IgG抗体的来源。通过使用这些单克隆抗体，我们已经鉴定了包膜蛋白gp 46 a.a.187-199上HTLV-1的主要线性中和B细胞表位。因此，我们提出该区域将是基于肽的HTLV-1疫苗的良好候选物。为了开发基于肽的疫苗，其可以诱导针对HTLV-1的高滴度的中和抗体，我们首先合成了含有HTLV-1 gp 46 a.a.187-199的主要中和决定簇的a.a.序列的各种长度的肽。用MAP 181 -210免疫不同品系的大鼠和家兔，均能诱导产生高滴度的中和抗体。我们还鉴定了不同品系大鼠中gp 46 a.a.194-210上的主要T细胞表位。此外，MAP 181 -210含有具有各种HLA单倍型的人类中a.a.194-210上的T细胞辅助表位。因此，MAP 181 -210可能成为用于人类的基于肽的疫苗的第一候选者之一。