Bazhan Sergei I, Karpenko Larisa I, Lebedev Leonid R, Uzhachenko Roman V, Belavin Pavel A, Eroshkin Alexey M, Ilyichev Alexander A
Theoretical Department, State Research Center of Virology and Biotechnology Vector, 630559 Koltsovo, Novosibirsk Region, Russia.
Mol Immunol. 2008 Feb;45(3):661-9. doi: 10.1016/j.molimm.2007.07.016. Epub 2007 Sep 14.
Immunogenic properties of the combined vaccine CombiHIVvac, comprising polyepitope HIV-1 immunogens, one being the artificial polyepitope protein TBI, containing the T- and B-cell epitopes from Env and Gag proteins, and the DNA vaccine construct pcDNA-TCI coding for the artificial protein TCI, carrying over 80 T-cell epitopes (both CD4+ CTL and CD8+ Th) from Env, Gag, Pol, and Nef proteins, are studied in this work. The data reported demonstrate clearly that a combination of two B- and T-cell immunogens (TBI and TCI) in one construct results in a synergistic increase in the antibody response to both TBI protein and the proteins from HIV-1 lysate. The level of antibodies induced by immunization with the constructs containing either immunogen alone (TBI protein or the plasmid pcDNA-TCI) was significantly lower as compared to that induced by the combined vaccine. The analysis performed suggests that the presence of CD4+ T-helper epitopes, which can be presented by MHC class II, in the protein TCI may be the main reason underlying the increased synthesis of antibodies to TBI protein due to a CD4-mediated stimulation of B-cell proliferation and differentiation.
本研究对联合疫苗CombiHIVvac的免疫原性进行了探讨。该联合疫苗包含多表位HIV-1免疫原,其中之一是人工多表位蛋白TBI,它含有来自Env和Gag蛋白的T细胞和B细胞表位;另一种是编码人工蛋白TCI的DNA疫苗构建体pcDNA-TCI,TCI携带来自Env、Gag、Pol和Nef蛋白的80多个T细胞表位(包括CD4+CTL和CD8+Th表位)。报告的数据清楚地表明,在一个构建体中结合两种B细胞和T细胞免疫原(TBI和TCI)会导致对TBI蛋白和HIV-1裂解物中的蛋白的抗体反应协同增加。与联合疫苗诱导的抗体水平相比,单独使用任何一种免疫原(TBI蛋白或质粒pcDNA-TCI)构建体免疫诱导的抗体水平显著较低。所进行的分析表明,蛋白TCI中存在可由MHC II类呈递的CD4+辅助性T细胞表位,可能是由于CD4介导的B细胞增殖和分化刺激导致针对TBI蛋白的抗体合成增加的主要原因。