Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1IIIB Gag-Pol-Nef proteins of clade B
Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1IIIB Gag-Pol-Nef proteins of clade B
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DOI：
10.1016/j.vaccine.2006.09.090
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发表时间：
2007-04-12
期刊：
影响因子：
5.5
通讯作者：
Esteban, Mariano
中科院分区：
文献类型：
--
作者：
Gomez, Carmen Elena;Najera, Jose Luis;Esteban, Mariano
在这项研究中，我们已经产生并确定了两种新的HIV/AIDS疫苗候选物的免疫原性，这两种疫苗候选物基于高度减毒的牛痘病毒株MVA和NYVAC，在相同的基因座（TK）和相同的病毒启动子下有效地表达编码进化枝B的gp 120和Gag-Pol-Nef抗原的密码子优化的HIV-1基因（称为MVA-B和NYVAC-B）。在感染的人HeLa细胞中，gp 120从细胞中释放，GPN作为多聚蛋白产生; NYVAC-B诱导严重的细胞凋亡，但MVA-B不诱导。两种痘病毒载体显示插入片段的遗传稳定性。在BALB/c和人类HLA-A2 1类转基因HHD小鼠中，两种载体都是有效的免疫原，并诱导针对四种HIV-1抗原中所代表的肽的广泛细胞免疫应答。在小鼠模型中的免疫应答的幅度和宽度方面观察到一些差异。在DNA初免/痘病毒加强方案中，在用NYVAC-B加强的BALB/c小鼠中获得了最强的免疫应答，如通过新鲜IFN-γ和IL-2 ELISPOT测量的，而在HHD小鼠中，痘病毒载体之间没有差异。当用同源或组合痘病毒载体进行初免/加强时，方案MVA-B/MVA-B和NYVAC-B/NYVAC-B或组合NYVAC-B/MVA-B在两种小鼠模型中产生最一致的更广泛的免疫应答，尽管DNA-B/痘病毒-B方案的总体应答的幅度更高。所有的免疫方案都诱导了针对来自HIV-1克隆LAV的gp 160蛋白的一些不道德应答。我们的研究结果表明，MVA-B和NYVAC-B符合标准，是潜在的有用的候选疫苗对艾滋病毒/艾滋病。(c)2006爱思唯尔有限公司保留所有权利。
In this investigation we have generated and defined the immunogenicity of two novel HIV/AIDS vaccine candidates based on the highly attenuated vaccinia virus strains, MVA and NYVAC, efficiently expressing in the same locus (TK) and under the same viral promoter the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef antigens of clade B (referred as MVA-B and NYVAC-B). In infected human HeLa cells, gp120 is released from cells and GPN is produced as a polyprotein; NYVAC-B induces severe apoptosis but not MVA-B. The two poxvirus vectors showed genetic stability of the inserts. In BALB/c and in transgenic HHD mice for human HLA-A2 class 1, both vectors are efficient immunogens and induced broad cellular immune responses against peptides represented in the four HIV-1 antigens. Some difference, were observed in the magnitude and breadth of the immune response in the Mouse models. In DNA prime/poxvirus boost protocols, the strongest immune response, as measured by fresh IFN-gamma and IL-2 ELISPOT, was obtained in BALB/c mice boosted with NYVAC-B, while in HHD mice there were no differences between the poxvirus vectors. When the prime/boost was performed with homologous or with combination of poxvirus vectors, the protocols MVA-B/MVA-B and NYVAC-B/NYVAC-B, or the combination NYVAC-B/MVA-B gave the most consistent broader immune response in both mouse models, although the magnitude of the overall response was higher for the DNA-B/poxvirus-B regime. All of the immunization protocols induced some Immoral response against the gp160 protein from HIV-1 clone LAV. Our findings indicate that MVA-B and NYVAC-B meet the criteria to be potentially useful vaccine candidates against HIV/AIDS. (c) 2006 Elsevier Ltd. All rights reserved.