Naylor P H, Sztein M B, Wada S, Maurer S, Holterman D, Kirkley J E, Naylor C W, Zook B C, Hitzelberg R A, Gibbs C J
Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC 20037.
Int J Immunopharmacol. 1991;13 Suppl 1:117-27. doi: 10.1016/0192-0561(91)90133-r.
Immunization with a synthetic HIV-1 p17 peptide analog (HGP-30; aa 85-115 of HIV p17), coupled to a carrier protein (KLH, keyhole limpet hemocyanin) given with alum as the adjuvant induces antibodies which cross-react with both HGP-30 and HIV p17 and clones of cytotoxic and helper T-cells which recognize HGP-30 and HIV p17. Proliferation of lymphocytes in response to HGP-30 has been observed in mice, in HIV-infected individuals and in healthy HIV-seronegative volunteers vaccinated with the p17-based synthetic peptide construct. Cytotoxic T-cell responses against EBV transformed, recombinant p17 pulsed targets were observed using antigen-expanded PBLs from HGP-30-KLH immunized individuals. These results are consistent with predictions that the HGP-30 domain of HIV p17 contains both T- and B-cell epitopes that are recognized by animals and humans. In preclinical toxicology studies in animals and in initial clinical trials in humans the synthetic peptide construct (HGP-30-KLH/alum) has been shown to be safe. This paper summarizes the preclinical immunogenicity and safety data for HGP-30-KLH and presents the initial results from the first Phase 1 clinical trial.
用与载体蛋白（钥孔血蓝蛋白，KLH）偶联的合成HIV-1 p17肽类似物（HGP-30；HIV p17的85-115位氨基酸）进行免疫接种，并以明矾作为佐剂，可诱导出与HGP-30和HIV p17均发生交叉反应的抗体，以及识别HGP-30和HIV p17的细胞毒性T细胞和辅助性T细胞克隆。在小鼠、感染HIV的个体以及接种基于p17的合成肽构建体的健康HIV血清阴性志愿者中，均观察到淋巴细胞对HGP-30的增殖反应。使用来自HGP-30-KLH免疫个体的抗原扩增外周血淋巴细胞（PBL），观察到针对EBV转化的、重组p17脉冲靶标的细胞毒性T细胞反应。这些结果与以下预测一致，即HIV p17的HGP-30结构域包含动物和人类均可识别的T细胞和B细胞表位。在动物的临床前毒理学研究和人类的初步临床试验中，合成肽构建体（HGP-30-KLH/明矾）已被证明是安全的。本文总结了HGP-30-KLH的临床前免疫原性和安全性数据，并展示了首次1期临床试验的初步结果。
