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猿猴免疫缺陷病毒(SIV)gp130寡聚体可保护恒河猴(猕猴)免受在T细胞上生长或离体衍生的SIVmac32H的感染。

Simian immunodeficiency virus (SIV) gp130 oligomers protect rhesus macaques (Macaca mulatta) against the infection with SIVmac32H grown on T-cells or derived ex vivo.

作者信息

Luke W, Coulibaly C, Dittmer U, Voss G, Oesterle R, Makoschey B, Sauermann U, Jurkiewicz E, Stahl-Henning C, Petry H, Hunsmann G

机构信息

Department of Virology and Immunology, German Primate Centre, Göttingen, Germany.

出版信息

Virology. 1996 Feb 15;216(2):444-50. doi: 10.1006/viro.1996.0082.

Abstract

The efficacy of three SIVmac32H gp130 vaccines was compared in rhesus monkeys. Three rhesus monkeys were each immunized over a period of 20 weeks with a total of 600 microgram virion-derived gp130 oligomers (O-gp130) mixed with keyhole limpet hemocyanin and emulsified with incomplete Freund's adjuvant. Three other monkeys were infected with 5 x 10(8) PFU of vaccinia virus wild type (VV-wt) while three additional animals received an equivalent dose of VV expressing the gp130 of SIVmac (VV-gp130). At Week 8, the two VV-wt animals received an additional immunization with 100 microgram O-gp130 each. All VV-infected animals then received booster immunizations at Weeks 12, 16, and 20 with a total of 300 microgram O-gp130 per animal. All animals along with two controls were challenged iv with 50 MID50 of T-cell-grown SIVmac32H at Week 22. Four weeks after the challenge and thereafter, both controls and one animal from either VV group were infected as demonstrated by polymerase chain reaction (PCR), virus isolation, and antibody response. In contrast, all O-gp130 animals and one animal each from the VV-wt and the VV-gp130 group were completely protected as shown by negative PCR and virus reisolation. One animal of the VV-gp130 group was partially protected, since it remained virus isolation negative but became PCR positive. All protected animals did not develop a secondary antibody response. Six months after the first challenge, the five completely protected animals were reimmunized twice 4 weeks apart with a total of 200 microgram O-gp130 per animal. Two weeks later, all animals were challenged with 5 MID50 of the SIVmac32H/spI prepared from the spleen of an immunized, but unprotected SIV-infected rhesus monkey. After the second challenge, all three control animals and one of the vaccinees become productively infected. In contrast, two animals were completely protected, one from the former O-gp130 and one from the former VV-gp130 group. One animal from the former VV-wt group was only DNA-PCR positive and thus partially protected. Therefore, immunization with virion-derived gp130 oligomers of SIVmac32H can confer protection against the infection with T-cell-grown SIVmac32H as well as the ex vivo isolate SIVmac32H/spI.

摘要

在恒河猴中比较了三种SIVmac32H gp130疫苗的效力。三只恒河猴在20周的时间里,每只均用总共600微克与钥孔戚血蓝蛋白混合并经不完全弗氏佐剂乳化的病毒粒子衍生的gp130寡聚体(O-gp130)进行免疫。另外三只猴子感染5×10⁸ PFU的野生型痘苗病毒(VV-wt),另有三只动物接受等量表达SIVmac gp130的痘苗病毒(VV-gp130)。在第8周时,两只感染VV-wt的动物各自额外接种100微克O-gp130。然后所有感染VV的动物在第12、16和20周接受加强免疫,每只动物总共接种300微克O-gp130。在第22周时,所有动物以及两只对照动物经静脉注射50个半数感染剂量(MID50)的T细胞培养的SIVmac32H进行攻击。攻击后四周及之后,通过聚合酶链反应(PCR)、病毒分离和抗体反应证明,两只对照动物以及来自任一VV组的一只动物被感染。相比之下,如PCR阴性和病毒再分离所示,所有O-gp130组动物以及来自VV-wt组和VV-gp130组的各一只动物得到了完全保护。VV-gp130组的一只动物得到部分保护,因为其病毒分离仍为阴性,但PCR呈阳性。所有得到保护的动物均未产生二次抗体反应。首次攻击六个月后,五只完全得到保护的动物每隔4周进行两次重新免疫,每只动物总共接种200微克O-gp130。两周后,所有动物用从一只免疫但未得到保护的感染SIV的恒河猴脾脏制备的5个MID50的SIVmac32H/spI进行攻击。第二次攻击后,三只对照动物和一名疫苗接种者被有效感染。相比之下,两只动物得到完全保护,一只来自原O-gp130组,一只来自原VV-gp130组。来自原VV-wt组的一只动物仅DNA-PCR呈阳性,因此得到部分保护。因此,用SIVmac32H的病毒粒子衍生的gp130寡聚体进行免疫可提供针对T细胞培养的SIVmac32H以及体外分离株SIVmac32H/spI感染的保护。

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