Department of Microbiology, Second Military Medical University, Shanghai 200433, China.
Vaccine. 2012 Mar 23;30(14):2453-61. doi: 10.1016/j.vaccine.2012.01.055. Epub 2012 Feb 11.
HIV-1 Tat has been identified as an attractive target for vaccine development and is currently under investigation in clinical trials as both a therapeutic and preventative vaccine for HIV-1. The Tat C-terminal region is of significant importance for its extracellular activity. In this study, we designed two recombinant Tat immunogens, Tat(B41-100N) and Tat(B41-100C), with two extended Tat C-terminal regions (41-100 aa) and compared their humoral immune response with native Tat. Interestingly, our results showed that Tat(B41-100C) elicited a higher antibody titer than Tat and Tat(B41-100N) in both mice and rabbits. The recombinant fusion protein-based epitope analysis showed that Tat(B41-100C) induced a remarkably enhanced humoral immune response against extended Tat C-terminal regions containing residues 38-100, 49-100 and 60-100. Our study demonstrates that the designed Tat(B41-100C) presents a designed immunogenicity that elicits enhanced Tat-specific antibodies especially against extended Tat C-terminal regions.
HIV-1 Tat 已被确定为疫苗开发的有吸引力的靶标,目前正在临床试验中作为 HIV-1 的治疗性和预防性疫苗进行研究。Tat C 端区域对其细胞外活性具有重要意义。在这项研究中,我们设计了两种重组 Tat 免疫原 Tat(B41-100N)和 Tat(B41-100C),它们具有两个扩展的 Tat C 端区域(41-100aa),并将其体液免疫反应与天然 Tat 进行了比较。有趣的是,我们的结果表明,与 Tat 和 Tat(B41-100N)相比,Tat(B41-100C)在小鼠和兔中均引起了更高的抗体滴度。基于重组融合蛋白的表位分析表明,Tat(B41-100C)诱导了针对包含残基 38-100、49-100 和 60-100 的扩展 Tat C 端区域的显著增强的体液免疫反应。我们的研究表明,设计的 Tat(B41-100C)具有设计的免疫原性,可引发针对扩展 Tat C 端区域的增强的 Tat 特异性抗体。