Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C
Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C
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DOI：
10.1016/j.vaccine.2006.11.051
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发表时间：
2007-03-01
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：
Elena Gomez, Carmen;Luis Najera, Jose;Esteban, Mariano
基于减毒痘苗病毒株MVA和NYVAC的重组体被认为是针对不同人类疾病的候选载体。在这项研究中，我们在BALB/c和转基因HHD小鼠中构建并鉴定了两个表达在单个密码子优化的HIV-1基因gp120和Gag-Pol-Nef(GPN)分支C多蛋白(简称MVA-C和NYVAC-Q)上的减毒痘病毒载体的免疫原性。在用MVA-C或NYVAC-C或DNA-C免疫并用痘病毒载体增强的HHD小鼠中，脾T细胞对跨越gp120/GPN的C分支多肽有广泛的反应，主要针对Gag-1、Env-1和Env-2肽库。用表达gp120/GPN的痘病毒载体的同源或异种组合或表达gp120/GPN的Semliki森林病毒(SFV)载体免疫BALB/c小鼠，免疫应答也很广泛，但免疫原性最强的是Env-1、GPN-1和GPN-2。根据所使用的方案，观察到不同的痘病毒载体在细胞免疫反应的大小上的差异。痘病毒载体诱导的特异性细胞免疫应答为Th1型。在HHD和BALB/c小鼠中，NYVAC对载体的细胞应答高于对MVA的细胞应答，但在痘病毒免疫的动物血清中观察到两种载体对病毒抗原的识别差异。这些结果证明了MVA-C和NYVAC-C作为针对HIV-1分支C的新型候选疫苗的免疫原性。(C)2006爱思唯尔有限公司。保留所有权利。
Recombinants based on the attenuated vaccinia virus strains MVA and NYVAC are considered candidate vectors against different human diseases. In this study we have generated and characterized in BALB/c and in transgenic HHD mice the immunogenicity of two attenuated poxvirus vectors expressing in a single locus (TK) the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef (GPN) polyprotein of clade C (referred as MVA-C and NYVAC-Q. In HHD mice primed with either MVA-C or NYVAC-C, or primed with DNA-C and boosted with the poxvirus vectors, the splenic T cell responses against clade C peptides spanning gp120/GPN was broad and mainly directed against Gag-1, Env-1 and Env-2 peptide pools. In BALB/c mice immunized with the homologous or the heterologous combination of poxvirus vectors or with Semliki forest virus (SFV) vectors expressing gp120/GPN, the immune response was also broad but the most immunogenic peptides were Env-1, GPN-1 and GPN-2. Differences in the magnitude of the cellular immune responses were observed between the poxvirus vectors depending on the protocol used. The specific cellular immune response triggered by the poxvirus vectors was Th1 type. The cellular response against the vectors was higher for NYVAC than for MVA in both HHD and BALB/c mice, but differences in viral antigen recognition between the vectors was observed in sera from the poxvirus-immunized animals. These results demonstrate the immunogenic potential of MVA-C and NYVAC-C as novel vaccine candidates against clade C of HIV-1. (c) 2006 Elsevier Ltd. All rights reserved.