Puaux Anne-Laure, Marsac Delphine, Prost Stéphane, Singh Mandal K, Earl Patricia, Moss Bernard, Le Grand Roger, Riviere Yves, Michel Marie-Louise
INSERM U 370, Carcinogenèse Hépatique et Virologie Moléculaire, Département de Médecine Moléculaire, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Vaccine. 2004 Sep 9;22(27-28):3535-45. doi: 10.1016/j.vaccine.2004.03.044.
Recent efforts to design an human immunodeficiency virus type 1 (HIV-1) vaccine candidate have focused on means of eliciting anti-viral T-cell responses. We tried to improve the immunogenicity of DNA vaccines by designing hybrid DNA constructs encoding hepatitis B surface antigen (HBsAg) fused to antigenic domains of simian/human immunodeficiency virus (SHIV 89.6P). Immunisation with hybrid DNA induced both effector and long-lasting precursor T-cells. Following boosting with a recombinant modified vaccinia Ankara (rMVA) producing full-length SIV and HIV antigens, it appeared that priming with hybrid DNA had increased virus-specific T-cell responses in terms of both the number of virus-specific IFN-gamma-secreting T-cells and virus-specific lymphoproliferation. After intrarectal challenge with SHIV 89.6P, immunised animals demonstrated early control of SHIV 89.6P replication and stable CD4+ T-cell counts.
近期设计1型人类免疫缺陷病毒（HIV-1）候选疫苗的努力聚焦于引发抗病毒T细胞反应的方法。我们试图通过设计编码与猿猴/人类免疫缺陷病毒（SHIV 89.6P）抗原结构域融合的乙型肝炎表面抗原（HBsAg）的杂交DNA构建体来提高DNA疫苗的免疫原性。用杂交DNA免疫可诱导效应T细胞和持久的前体T细胞。在用产生全长SIV和HIV抗原的重组改良安卡拉痘苗病毒（rMVA）加强免疫后，似乎用杂交DNA进行初免在病毒特异性IFN-γ分泌T细胞数量和病毒特异性淋巴细胞增殖方面都增加了病毒特异性T细胞反应。在用SHIV 89.6P进行直肠内攻击后，免疫动物表现出对SHIV 89.6P复制的早期控制和稳定的CD4+ T细胞计数。
