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基于免疫刺激复合物(ISCOM)技术、使用包膜和GAG基因产物的HIV实验性疫苗。

HIV experimental vaccines based on the iscom technology using envelope and GAG gene products.

作者信息

Akerblom L, Nara P, Dunlop N, Putney S, Morein B

机构信息

National Veterinary Institute, Department of Virology, Uppsala, Sweden.

出版信息

Biotechnol Ther. 1993;4(3-4):145-61.

PMID:8292967
Abstract

In previous experiments gp160 incorporated into iscom was shown to induce neutralizing antibodies to the homologous as well as the heterologous isolates of HIV-1 (Akerblom et al., AIDS Res., 1991). In the present work we have incorporated into iscoms three defined recombinant DNA products of HIV-1. The carboxy-terminal part of gp120 expressed in E. Coli-PB-1; a chimera containing parts of both p24 and p15 expressed in E. coli-GAG; and baculovirus gp160 cloned in baculovirus and produced in insect cells. Immune responses were induced by the iscom preparations to the homologous antigen as well as to defined recombinant products and to the synthetic peptide RP135 (aa 304-328) harboring a neutralizing epitope. Sera from mice immunized with PB1-iscoms and gp160 (baculo) iscoms were tested in a syncytie inhibition assay. The serum from a mouse immunized with PB1 iscoms reacted strongly with the synthetic peptide RP135 and also neutralized the homologous isolate HIV-1/IIIB with a neutralization titer of 1/64. Three gp160 (baculo) iscom antisera were tested, of which two reacted strongly with the synthetic peptide RP135 but did not neutralize the homologous isolate HIV-1/IIIB. High serum titers were induced in mice by the gp160 iscoms (2 micrograms) to homologous antigen and the recombinant DNA E. coli construct p121 covering part of gp41. The ceilings of the antibody responses were reached after two immunizations. The PB1- and GAG-iscoms required three immunizations to reach the ceiling of the antibody response.

摘要

在先前的实验中,已证明掺入iscom的gp160能诱导针对HIV-1同源及异源分离株的中和抗体(阿克布洛姆等人,《艾滋病研究》,1991年)。在本研究中,我们将三种明确的HIV-1重组DNA产物掺入iscom中。在大肠杆菌-PB-1中表达的gp120羧基末端部分;在大肠杆菌-GAG中表达的包含p24和p15部分的嵌合体;以及克隆于杆状病毒并在昆虫细胞中产生的杆状病毒gp160。iscom制剂能诱导针对同源抗原、明确的重组产物以及含有中和表位的合成肽RP135(氨基酸304 - 328)的免疫反应。用PB1-iscom和gp160(杆状病毒)iscom免疫的小鼠血清在细胞融合抑制试验中进行检测。用PB1 iscom免疫的小鼠血清与合成肽RP135强烈反应,并且还以1/64的中和效价中和同源分离株HIV-1/IIIB。检测了三种gp160(杆状病毒)iscom抗血清其中两种与合成肽RP135强烈反应,但未中和同源分离株HIV-1/IIIB。gp160 iscom(2微克)在小鼠中诱导了针对同源抗原和覆盖gp41部分的重组DNA大肠杆菌构建体p121的高血清滴度。两次免疫后达到抗体反应的峰值。PB1-和GAG-iscom需要三次免疫才能达到抗体反应的峰值。

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