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用人类免疫缺陷病毒包膜糖蛋白gp120免疫的黑猩猩(黑猩猩属)面临的挑战。

Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120.

作者信息

Arthur L O, Bess J W, Waters D J, Pyle S W, Kelliher J C, Nara P L, Krohn K, Robey W G, Langlois A J, Gallo R C

机构信息

Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.

出版信息

J Virol. 1989 Dec;63(12):5046-53. doi: 10.1128/JVI.63.12.5046-5053.1989.

Abstract

The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 10(4) was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gp120 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gp120-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gp120 formulated in alum was not effective in preventing infection with HIV-1.

摘要

1型人类免疫缺陷病毒(HIV-1)是获得性免疫缺陷综合征的病原体,可感染人类和黑猩猩。为了确定免疫接种预防感染的效果,用从感染了III B型人类嗜T细胞病毒(HTLV-IIIB)的细胞膜中纯化的gp120对黑猩猩进行免疫接种,并用同源病毒HTLV-IIIB进行攻击。通过使用在H9细胞中产生的未浓缩的HTLV-IIIB制备HTLV-IIIB攻击毒株。测定了该毒株在人类和黑猩猩外周血单核细胞以及人类淋巴样细胞系中的病毒滴度;确定其细胞培养感染性为10(4)。所有静脉接种40个或更多细胞培养感染单位的黑猩猩都被感染,病毒分离和血清转化证明了这一点。接种4个细胞培养感染单位的两只黑猩猩中有一只被感染。用明矾配制的gp120免疫的黑猩猩产生了能沉淀gp120并中和HTLV-IIIB的抗体。与未接种疫苗和未感染HIV的黑猩猩的外周血单核细胞相比,来自接种gp120疫苗和感染HIV的动物的外周血单核细胞在HIV蛋白增殖试验中的反应明显更强。用明矾配制的gp120免疫的两只黑猩猩用HTLV-IIIB毒株的病毒进行攻击。一只动物接受400个细胞培养感染单位,另一只接受40个感染单位。两只动物都感染了HIV,这表明用明矾配制的gp120免疫引发的免疫反应在预防HIV-1感染方面无效。

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