Liu Qiang, Li Yue, Luo Zhenwu, Yang Guibo, Liu Yong, Liu Ying, Sun Maosheng, Dai Jiejie, Li Qihan, Qin Chuan, Shao Yiming
aState Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention bNational Institutes for Food and Drug Control, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing cCollege of Life Science, Nankai University, Tianjin dInstitute of Medical Biology, CAMS, Kunming eInstitute of Laboratory Animal Sciences, CAMS, Beijing fCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. *Drs Qiang Liu, Yue Li and Zhenwu Luo contributed equally to the writing of this article.
AIDS. 2015 Mar 27;29(6):649-58. doi: 10.1097/QAD.0000000000000595.
To assess the efficacy of HIV vaccines constructed from replication-competent Tiantan vaccinia virus (rTV) alone or combined with DNA in protecting Chinese rhesus macaques from homologous Simian/Human Immunodeficiency Virus (SHIV)-CN97001 challenge.
The nef, gag, pol, and gp140 genes from strain CRF07_BC HIV-1 CN54 were selected to construct an HIV vaccine using the rTV or rTV/DNA vaccine. After vaccination, the vaccine and control groups were intravenously challenged with SHIV-CN97001 (32 MID50). HIV-specific antibodies and neutralizing antibodies, gp70 V1V2 binding antibodies, and cytotoxic T-lymphocyte responses were measured prospectively after vaccination with an ELISA, a virus infectivity assay in TZM-bl cells, and ELISPOT assays, respectively. Viral RNA was quantified after challenge with real-time reverse transcriptase-PCR (RT-PCR), and protection efficacy was determined with an analysis of CD8 lymphocyte depletion in vivo.
Both rTV and DNA/rTV vaccine groups developed strong cellular and humoral responses against HIV-1 CN54 antigens, including Gag and Env, and also developed significant and persistent anti-Env antibodies and neutralizing antibodies after immunization. Both the rTV and DNA/rTV groups were significantly protected against SHIV-CN97001 or displayed lower viremia than the controls. After CD8 lymphocyte depletion, no viremia was detectable in the vaccinated monkeys, but rebounded rapidly in the control animals. Protection against infection correlated with vaccine-elicited neutralizing antibodies specific for homologous HIV-1 viruses.
An rTV-based HIV-1 vaccine, with or without a DNA primer, provided protection from SHIV challenge in a macaque model. Replication-competent Tiantan vaccinia is a promising vector and should enable advances in HIV-1 vaccine development.
评估单独使用具有复制能力的天坛痘苗病毒（rTV）构建的HIV疫苗或与DNA联合构建的HIV疫苗，在保护中国恒河猴免受同源猿猴/人类免疫缺陷病毒（SHIV）-CN97001攻击方面的效果。
选择来自CRF07_BC HIV-1 CN54毒株的nef、gag、pol和gp140基因，使用rTV或rTV/DNA疫苗构建HIV疫苗。接种疫苗后，疫苗组和对照组静脉注射SHIV-CN97001（32个半数感染剂量50）进行攻击。接种疫苗后，分别通过酶联免疫吸附测定（ELISA）、TZM-bl细胞中的病毒感染性测定和酶联免疫斑点测定（ELISPOT），前瞻性地检测HIV特异性抗体和中和抗体、gp70 V1V2结合抗体以及细胞毒性T淋巴细胞反应。攻击后，使用实时逆转录聚合酶链反应（RT-PCR）对病毒RNA进行定量，并通过体内CD8淋巴细胞耗竭分析确定保护效果。
rTV疫苗组和DNA/rTV疫苗组均产生了针对HIV-1 CN54抗原（包括Gag和Env）的强烈细胞和体液反应，免疫后还产生了显著且持久的抗Env抗体和中和抗体。rTV疫苗组和DNA/rTV疫苗组均受到SHIV-CN97001的显著保护，或显示出比对照组更低的病毒血症。CD段8淋巴细胞耗竭后，接种疫苗的猴子中未检测到病毒血症，但对照动物中的病毒血症迅速反弹。对感染的保护与疫苗诱导的针对同源HIV-1病毒的中和抗体相关。
基于rTV的HIV-1疫苗，无论有无DNA引物，在猕猴模型中均能提供免受SHIV攻击的保护。具有复制能力的天坛痘苗病毒是一种有前景的载体，应能推动HIV-1疫苗研发取得进展。
