Kalus R M, Kantor J A, Gritz L, Gómez Yafal A, Mazzara G P, Schlom J, Hodge J W
Howard Hughes Medical Institute, Research Scholar's Program at the NIH, Bethesda, MD 20892, USA.
Vaccine. 1999 Feb 26;17(7-8):893-903. doi: 10.1016/s0264-410x(98)00275-8.
Several recombinant vaccinia viruses are currently being evaluated to induce antigen-specific immunity to a variety of infectious disease agents and tumor associated antigens. T-cell costimulation is extremely important in enhancing T-cell responses, and recombinant vaccines have now been shown to be effective vectors to express a range of these molecules. Both combination vaccines (an admixture of a recombinant vaccinia virus expressing a specific target antigen and a recombinant vaccinia virus expressing a costimulatory molecule) and dual-gene vaccines expressing both transgenes on the same vector have been shown capable of effectively enhancing antigen-specific responses via T-cell costimulation. In this report, we compare for the first time the use of both types of approaches to enhance antigen-specific T-cell responses, and we demonstrate the importance of route of vaccine administration and vaccine dose in attaining optimal T-cell responses. These studies should have direct bearing on the design of vaccine clinical trials for infectious agents and/or tumor associated antigens, in which T-cell costimulatory molecules will be employed to enhance antigen-specific T-cell responses via the use of either combination or dual-gene vaccinia vaccines.
目前正在评估几种重组痘苗病毒，以诱导针对多种传染病病原体和肿瘤相关抗原的抗原特异性免疫。T细胞共刺激在增强T细胞反应中极其重要，并且重组疫苗现已被证明是表达一系列此类分子的有效载体。组合疫苗（表达特定靶抗原的重组痘苗病毒与表达共刺激分子的重组痘苗病毒的混合物）和在同一载体上表达两种转基因的双基因疫苗都已显示能够通过T细胞共刺激有效地增强抗原特异性反应。在本报告中，我们首次比较了使用这两种方法增强抗原特异性T细胞反应的情况，并且我们证明了疫苗接种途径和疫苗剂量在获得最佳T细胞反应中的重要性。这些研究对于传染病病原体和/或肿瘤相关抗原的疫苗临床试验设计应该具有直接影响，在这些试验中，将通过使用组合或双基因痘苗疫苗来利用T细胞共刺激分子增强抗原特异性T细胞反应。
