Hone D M, Lewis G K, Beier M, Harris A, McDaniels T, Fouts T R
Department of Geographic Medicine, School of Medicine, University of Maryland, Baltimore.
Dev Biol Stand. 1994;82:159-62.
Human immunodeficiency virus is known to enter the host at parenteral and mucosal sites and consequently an effective vaccine should stimulate immunity at both routes of entry. One approach toward stimulating HIV-specific mucosal and systemic immunity is the use of candidate live oral Salmonella typhi vector vaccine, strain CVD 908, which has been shown to stimulate mucosal and systemic immunity in volunteers. Using recombinant DNA techniques we constructed an expression cassette which comprises the lpp promoter (Plpp) and sequences encoding recombinant gp120 (rgp120). When the Plpp-rgp120 expression cassette is integrated into the chromosome of CVD 908 in the delta aroC allele, high levels of recombinant gp120 expression are observed. It is likely that effective immunity against HIV in humans will require immunization with multiple HIV antigens. Hence, a second expression cassette encoding two additional HIV antigens with vaccine potential, p24 (a HIV-1 gag gene product) and Nef (a putative regulator of HIV-1 gene expression) has been constructed. We plan to integrate the p24-Nef-encoding expression cassette into the aroD locus in the chromosome of CVD 908 delta aroC::rgp120 in a stable manner to produce a CVD 908-HIV vector vaccine that expresses multiple HIV antigens.
已知人类免疫缺陷病毒可经肠外和黏膜部位进入宿主，因此有效的疫苗应能在这两种进入途径刺激免疫反应。一种刺激HIV特异性黏膜和全身免疫的方法是使用候选活口服伤寒沙门氏菌载体疫苗CVD 908株，该疫苗已被证明能在志愿者中刺激黏膜和全身免疫。我们利用重组DNA技术构建了一个表达盒，其包含lpp启动子（Plpp）和编码重组gp120（rgp120）的序列。当Plpp-rgp120表达盒整合到CVD 908的aroC基因缺失等位基因的染色体中时，可观察到高水平的重组gp120表达。对人类而言，有效的抗HIV免疫可能需要用多种HIV抗原进行免疫接种。因此，已构建了第二个表达盒，其编码另外两种具有疫苗潜力的HIV抗原，即p24（一种HIV-1 gag基因产物）和Nef（一种假定的HIV-1基因表达调节因子）。我们计划将编码p24-Nef的表达盒以稳定的方式整合到CVD 908 delta aroC::rgp120染色体的aroD位点，以生产一种表达多种HIV抗原的CVD 908-HIV载体疫苗。
