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HIV PREVENTIVE VACCINE BASED ON HIV-SPECIFIC ANTIBODIES

机译:基于HIV特异性抗体的HIV预防疫苗

摘要

1. A method of obtaining an HIV vaccine that prevents the development of infection by immunizing uninfected people, comprising the steps of:! i) creation of a phagemid library of monoclonal antibodies, the sequences of which are contained in mRNA of B-lymphocytes obtained from several patients infected with HIV-1 subtype A or B,! ii) enrichment of the phagemid antibody library with panning on native or recombinant HIV-1 peptides,! iii) collection of HIV-1 peptide / polypeptide / protein material by reverse panning using an HIV-1 specific phagemid library mounted on a solid support! iv) identification and quantification of the peptide material obtained in step iii) and its variability using mass spectrometric (PEAKS-LC-MS) analysis and! (v) using the results of the analysis of step iv) to obtain glycosylated recombinant HIV-1 env peptides in an inducible expression system with eukaryotic glycosylation (Leishmania tarentolae, yeast),! (vi) purification of recombinant HIV-1 env peptides and preparation of an immunoactivating composition for vaccination using a suitable adjuvant as a delivery system (sterically stabilized liposomes, virosomes). ! 2. The method according to claim 1, wherein the HIV carriers used to produce the biomaterial are infected with HIV of one or different subtypes. ! 3. The method according to claim 1, in which HIV-infected to obtain viral material can be both untreated and treated with antiretroviral drugs. ! 4. The method according to claim 1, when the resulting viral material of a cohort of HIV-infected multiplies as a pool (many
机译:1.一种获得HIV疫苗的方法,该方法通过对未感染者进行免疫来防止感染的发展,包括以下步骤: i)创建单克隆抗体的噬菌粒文库,其序列包含在从感染了HIV-1亚型A或B的几名患者获得的B淋巴细胞的mRNA中! ii)通过淘选天然或重组HIV-1肽来丰富噬菌粒抗体文库! iii)使用安装在固体支持物上的HIV-1特异性噬菌粒文库通过逆向淘选收集HIV-1肽/多肽/蛋白质材料! iv)使用质谱分析法(PEAKS-LC-MS)对步骤iii)中获得的肽材料及其可变性进行鉴定和定量! (v)使用步骤iv)的分析结果,在具有真核糖基化的诱导型表达系统中(糖化利什曼原虫,酵母)获得糖基化的重组HIV-1 env肽! (vi)使用合适的佐剂作为递送系统(空间稳定的脂质体,病毒体)纯化重组HIV-1 env肽并制备用于疫苗接种的免疫活化组合物。 ! 2.根据权利要求1所述的方法,其中,用于生产所述生物材料的HIV携带者被一种或不同亚型的HIV感染。 ! 3.根据权利要求1的方法,其中感染HIV以获得病毒材料的病毒既可以未经治疗也可以用抗逆转录病毒药物治疗。 ! 4.如权利要求1所述的方法,其特征在于,当一组HIV感染者的所得病毒物质成倍增加时(许多

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