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

我们用EB病毒转化B淋巴细胞，产生了许多人抗HTLV-1的单抗(MAb)。从HAM/TSP患者的外周血中获得了致力于产生抗HTLV-1抗体的B淋巴细胞。利用这些单抗，我们确定了HTLV-1在包膜蛋白gp46 a.a.187-199上的主要线性中和B细胞表位。因此，我们提出该区域可能是基于多肽的HTLV-1疫苗的一个很好的候选区域。为了开发一种能诱导高滴度中和抗体的多肽疫苗，我们首先合成了含有HTLV-1 gp46 a.a.187-199主要中和决定簇的不同长度的多肽。用MAP181-210免疫不同品系的大鼠和兔，诱导产生高滴度的中和抗体。我们还在不同品系的大鼠中鉴定了gp46 a.194-210上的主要T细胞表位。此外，在具有不同单倍型的人类中，MAP181-210含有a.194-210上的T细胞辅助表位。因此，MAP181-210有可能成为人类使用的多肽疫苗的首批候选疫苗之一。

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.