接受HIV-1中和性单克隆抗体被动免疫治疗患者的免疫学和病毒学相互作用

J Hinkula, G Bratt, G Gilljam, S Nordlund, P A Broliden, V Holmberg, E Olausson-Hansson, J Albert, E Sandström, B Wahren
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引用次数: 0

摘要

采用高人类免疫缺陷病毒1型(HIV-1)中和滴度的小鼠单克隆抗体对11例晚期hiv感染患者进行被动免疫治疗。5例患者血清核心蛋白p24水平下降,5例患者血清核心蛋白p24水平保持不变。定量聚合酶链反应(PCR)测定血浆病毒RNA水平,4例下降,4例稳定,3例上升。8例患者出现抗小鼠(HAMA)反应,6例出现抗独特型抗体。治疗期间在患者血清中形成的免疫复合物显示主要含有包膜糖蛋白gp120,在11名接受治疗的患者中,有9名患者在治疗结束时减少。6例患者在免疫治疗期间检测到抑制gp120结合CD4的抗体或抗体升高。对HIV-1 IIIB和MN株进行了HIV-1 V3区血清学研究,治疗后滴度或贪婪度没有或非常小的变化。在终止治疗前后收集的血清样品中,未观察到HTLVIIIB菌株的中和效价变化。在11名患者中,有9名患者被植物血凝素(PHA)激活后,体外T淋巴细胞增殖的刺激比治疗前有所增加。多种抗原如HIV-1重组抗原、巨细胞病毒(CMV)、破伤风类毒素(TT)和纯化的结核分枝杆菌(PPD)蛋白衍生物也能增加t细胞的增殖。这些发现表明血清中gp120的总含量降低,使t细胞活化更好。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies.

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.

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