Sun Caijun, Zhang Yinfeng, Liu Yichu, Zhang Maochao, Chen Ling
Center for Infection & Immunity, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, China.
AIDS Res Hum Retroviruses. 2011 Jun;27(6):681-6. doi: 10.1089/AID.2010.0210. Epub 2011 Jan 8.
Adenovirus (Ad) is still under extensive investigation as a vector for HIV vaccination; however, one possible explanation for the failure of Merck's STEP trial is the relatively weak immunogenicity of replication-defective Ad vectors. In this study, a novel strategy to enhance the immunogenicity of replication-defective Ad-based HIV vaccines was developed. First, a recombinant plasmid expressing adenoviral E1 protein (pVAX-E1) was constructed to complement the E1-deleted replication-defective Ad vectors in trans. Then, the immunogenicity of the vaccine regimen of Ad5-HIV gag plus pVAX-E1 plasmid was assessed in rhesus macaques. Compared with traditional administration of Ad-based vectors alone, the results showed that our strategy elicited a more sustained and robust HIV gag-specific cellular response and enhanced long-term proliferation of CD4(+) and CD8(+) T lymphocytes. This strategy represents a proof-of-concept that enhances the immunogenicity of replication-defective Ad-based vectors, and it exemplifies the useful implications for Ad-based HIV vaccines and other vaccines.
腺病毒（Ad）作为一种用于HIV疫苗接种的载体仍在广泛研究中；然而，默克公司STEP试验失败的一个可能原因是复制缺陷型Ad载体的免疫原性相对较弱。在本研究中，开发了一种增强基于复制缺陷型Ad的HIV疫苗免疫原性的新策略。首先，构建了表达腺病毒E1蛋白的重组质粒（pVAX-E1），以反式互补缺失E1的复制缺陷型Ad载体。然后，在恒河猴中评估了Ad5-HIV gag加pVAX-E1质粒疫苗方案的免疫原性。与单独传统给药基于Ad的载体相比，结果表明我们的策略引发了更持久、更强的HIV gag特异性细胞反应，并增强了CD4(+)和CD8(+) T淋巴细胞的长期增殖。该策略代表了一种增强基于复制缺陷型Ad的载体免疫原性的概念验证，并且它例证了对基于Ad的HIV疫苗和其他疫苗的有益启示。
