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HIV-1 p17合成肽疫苗HGP-30:在人体受试者中诱导免疫反应及在严重联合免疫缺陷小鼠中抵御HIV攻击的初步保护证据

HIV-1 p17 synthetic peptide vaccine HGP-30: induction of immune response in human subjects and preliminary evidence of protection against HIV challenge in SCID mice.

作者信息

Sarin P S, Mora C A, Naylor P H, Markham R, Schwartz D, Kahn J, Heseltine P, Gazzard B, Youle M, Rios A

机构信息

Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, D.C. 20037, USA.

出版信息

Cell Mol Biol (Noisy-le-grand). 1995 May;41(3):401-7.

PMID:7580834
Abstract

An HIV-1 p17 subunit vaccine, HGP-30, was evaluated in 38 HIV-1 seronegative individuals in phase I clinical trials in U.K. and U.S.A. The vaccine preparation induced cytotoxic T-cell (CTL) (11/25) and lymphocyte proliferation responses to KLH (19/20) and HGP-30/p17 (24/29) as well as antibody responses to HGP-30 (29/38) and KLH (38/38). The CTL activity was observed in a higher number of vaccine recipients (9/18) in the lower dose groups (10 and 25 micrograms/kg) than the vaccine recipients (2/7) in the 50 and 100 micrograms/kg dose group. These observations suggest that the 10-25 micrograms/kg vaccine dose may preferentially induce TH1 cell responses. TH1 cell responses have been suggested as important in inducing protective cell mediated immunity. The CTL response has been shown to be CD8+. In a pilot study in SCID mice, HIV-1 virus challenge studies in mice reconstituted with cells from an HGP-30 immunized individual showed protection against virus challenge as compared to SCID mice reconstituted with cells from a non-immunized subject. These studies suggest that HGP-30 is capable of inducing protective cellular immunity.

摘要

一种HIV-1 p17亚基疫苗HGP-30,在英国和美国进行的I期临床试验中,对38名HIV-1血清阴性个体进行了评估。该疫苗制剂诱导了细胞毒性T细胞(CTL)反应(11/25)、对钥孔戚血蓝蛋白(KLH)(19/20)和HGP-30/p17(24/29)的淋巴细胞增殖反应,以及对HGP-30(29/38)和KLH(38/38)的抗体反应。在较低剂量组(10和25微克/千克)中,观察到有更多的疫苗接种者(9/18)出现CTL活性,而在50和100微克/千克剂量组中,只有2/7的疫苗接种者出现该活性。这些观察结果表明,10 - 25微克/千克的疫苗剂量可能优先诱导TH1细胞反应。TH1细胞反应被认为在诱导保护性细胞介导免疫中很重要。CTL反应已被证明是CD8 +。在一项针对严重联合免疫缺陷(SCID)小鼠的初步研究中,与用未免疫个体的细胞重建的SCID小鼠相比,用来自HGP-30免疫个体的细胞重建的小鼠进行HIV-1病毒攻击研究显示出对病毒攻击的保护作用。这些研究表明,HGP-30能够诱导保护性细胞免疫。

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