Wild Jens, Bieler Kurt, Köstler Josef, Frachette Marie-Joelle, Jeffs Simon, Vieira Sueli, Esteban Mariano, Liljeström Peter, Pantaleo Guiseppe, Wolf Hans, Wagner Ralf
Institute of Medical Microbiology, University of Regensburg, Regensburg, Germany.
Viral Immunol. 2009 Oct;22(5):309-19. doi: 10.1089/vim.2009.0038.
As part of a European initiative (EuroVacc), we report the design, construction, and immunogenicity of two HIV-1 vaccine candidates based on a clade C virus strain (CN54) representing the current major epidemic in Asia and parts of Africa. Open reading frames encoding an artificial 160-kDa GagPolNef (GPN) polyprotein and the external glycoprotein gp120 were fully RNA and codon optimized. A DNA vaccine (DNA-GPN and DNA-gp120, referred to as DNA-C), and a replication-deficient vaccinia virus encoding both reading frames (NYVAC-C), were assessed regarding immunogenicity in Balb/C mice. The intramuscular administration of both plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial T-cell responses against both antigens as well as Env-specific antibodies. Whereas low doses of NYVAC-C failed to induce specific CTL or antibodies, high doses generated cellular as well as humoral immune responses, but these did not reach the levels seen following DNA vaccination. The most potent immune responses were detectable using prime:boost protocols, regardless of whether DNA-C or NYVAC-C was used as the priming or boosting agent. These preclinical findings revealed the immunogenic response triggered by DNA-C and its enhancement by combining it with NYVAC-C, thus complementing the macaque preclinical and human phase I clinical studies of EuroVacc.
作为一项欧洲计划（EuroVacc）的一部分，我们报告了两种基于C亚型病毒株（CN54）的HIV-1疫苗候选物的设计、构建及其免疫原性，该病毒株代表了当前在亚洲和非洲部分地区流行的主要毒株。编码人工160 kDa GagPolNef（GPN）多蛋白和外膜糖蛋白gp120的开放阅读框经过了全RNA和密码子优化。对一种DNA疫苗（DNA-GPN和DNA-gp120，称为DNA-C）以及一种编码这两个阅读框的复制缺陷型痘苗病毒（NYVAC-C）在Balb/C小鼠中的免疫原性进行了评估。两种质粒DNA构建体经肌肉注射，随后进行两次加强DNA免疫，诱导了针对两种抗原以及Env特异性抗体的强烈T细胞应答。低剂量的NYVAC-C未能诱导特异性CTL或抗体，而高剂量则产生了细胞免疫和体液免疫应答，但这些应答未达到DNA疫苗接种后的水平。无论使用DNA-C还是NYVAC-C作为初免或加强免疫剂，使用初免：加强免疫方案均可检测到最有效的免疫应答。这些临床前研究结果揭示了DNA-C引发的免疫应答以及将其与NYVAC-C联合使用后的增强效果，从而补充了EuroVacc的猕猴临床前研究和人类I期临床研究。
