余双庆;冯霞;刘红梅;杨海儒;李红霞;曾毅;

• 1:中国疾病预防控制中心病毒病预防控制所传染病预防控制国家重点实验室

摘要(Abstract)：

本文旨在研究表达HIV-1中国流行株gp120基因的重组腺相关病毒疫苗在小鼠和恒河猴体内的免疫原性。用rAAV2/1-gp120免疫BALB/c小鼠和恒河猴,分别用ELISA和HIV-1假病毒中和试验检测免疫动物血清中HIV-1特异性IgG抗体水平和中和抗体水平,用ELISPOT方法和体内杀伤实验检测HIV-1特异性细胞免疫应答水平。结果显示在小鼠体内用rAAV2/1-gp120仅免疫一次就能诱导较高水平的IgG抗体,IgG抗体至少能持续21周,但没有检测到中和抗体。rAAV2/1-gp120在小鼠体内诱导微弱水平的HIV-1特异性细胞免疫应答。rAAV2/1-gp120在恒河猴体内诱导的HIV-1特异性细胞和抗体反应均很弱,且检测不到中和抗体。提示rAAV2/1载体在诱导抗体反应方面具有特殊优势,但若希望诱导HIV-1特异性中和抗体,则需要改造env基因以提高其免疫原性。

关键词(KeyWords)： HIV-1;包膜糖蛋白Gp120;重组腺相关病毒;免疫原性

Abstract:

Keywords:

基金项目(Foundation): 国家重大科技专项(2008ZX10001-009);; 国家自然科学基金(30872397)

作者(Authors): 余双庆;冯霞;刘红梅;杨海儒;李红霞;曾毅;

DOI: 10.13242/j.cnki.bingduxuebao.002066

参考文献(References)：

• [1]Ready T.AIDSVAX flop leaves vaccine field unscathed[J].Nat Med,2003,9(4):376.
• [2]Wang S,Kennedy J S,West K,et al.Cross-subtype an-tibody and cellular i mmune responses induced by a poly-valent DNApri me-protein boost HIV-1vaccinein healthy human volunteers[J].Vaccine,2008,26(31):3947-3957.
• [3]刘红梅,余双庆,冯霞,等.1型和2型外壳蛋白构建的AAV载体携带HIV-1gag诱导免疫反应的比较研究[J].病毒学报,2007,23(3):177-182.
• [4]余双庆,冯霞,陈国敏,等.HIV-1B亚型gp120基因密码子优化前后免疫原性的比较[J].病毒学报,2004,20(3):214-217.
• [5]van der Meide P H,Groenestein R J,de Labie M C,et al.Enumeration of lymphokine-secreting cells as a quan-titative measure for cellular i mmune responses in Rhesus macaques[J].J Med Pri matol,1995,24(4):271-281.
• [6]Brockstedt D G,Podsakoff G M,Fong L,et al.Induc-tion of i mmunity to antigens expressed by recombinant adeno-associated virus depends on the route of adminis-tration[J].Clin I mmunol,1999,92(1):67-75.
• [7]Pitisuttithum P.HIV-1prophylactic vaccine trials in Thailand[J].Curr HIV Res,2005,3(1):17-30.
• [8]Lin S W,Hensley S E,Tatsis N,et al.Recombinant adeno-associated virus vectors induce functionally i m-paired transgene product-specific CD8+T cells in mice[J].J Clin Invest,2007,117(12):3958-3970.
• [9]Kiepiela P,Ngumbela K,Thobakgale C,et al.CD8+T-cell responses to different HIV proteins have discordant associations with viral load[J].Nat Med,2007,13(1):46-53.
• [10]Kwong P D,Wyatt R,Robinson J,et al.Structure of an HIV gp120envelope glycoprotein in complex with the CD4receptor and a neutralizing human antibody[J].Nature,1998,393(6686):648-659.
• [11]Chen B,Vogan E M,Gong H,et al.Structure of an unliganded si mian i mmunodeficiency virus gp120core[J].Nature,2005,433(7028):834-841.
• [12]Walker L M,Phogat S K,Chan-Hui P Y,et al.Broadand potent neutralizing antibodies froman African donor reveal a new HIV-1vaccine target[J].Science,2009,326(5950):285-289.