Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho Maklaya 16/10, Moscow 119334, Russia.
Mol Immunol. 2009 Nov;47(1):87-95. doi: 10.1016/j.molimm.2008.12.020. Epub 2009 Feb 6.
Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.
尽管人们付出了巨大努力，但是至今仍未成功研制出有效的 HIV 感染疫苗。HIV 利用复杂机制逃避宿主免疫系统杀伤的能力，给抗病毒治疗药物的开发带来了巨大的挑战。HIV 感染是通过包膜病毒糖蛋白 gp120 三聚体与淋巴细胞 CD4(+)受体相互作用而进行的。因此，该表面抗原可被视为免疫治疗的一个有利靶点。在本研究中，我们开发了三种不同策略，以在自身免疫倾向的小鼠（SJL 品系）中产生 gp120 特异性反应，作为产生“催化疫苗”的潜在工具。因此：（i）通过肽基膦酸盐（包膜糖蛋白的结构部分）进行反应性免疫接种，（ii）通过工程化融合的 gp120 和致脑炎肽（髓鞘碱性蛋白的一部分）表位进行免疫接种，和（iii）通过 DNA 联合疫苗接种和相应的 gp120 片段包封在脂质体中进行免疫接种。在前两种情况下，对单克隆抗体及其具有氨肽酶和 gp120 特异性蛋白水解活性的重组片段进行了表征。在后一种情况下，在细胞系模型中证明具有病毒中和活性的催化抗体被收获。
