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首页> 外文期刊>Vaccine >Membrane bound Indian Glade C HIV-1 envelope antigen induces antibodies to diverse and conserved epitopes upon DNA prime/protein boost in rabbits
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Membrane bound Indian Glade C HIV-1 envelope antigen induces antibodies to diverse and conserved epitopes upon DNA prime/protein boost in rabbits

机译：膜结合的Indian Glade C HIV-1包膜抗原在兔DNA初免/蛋白质增强后诱导针对多种保守表位的抗体

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The partial success of RV144 human clinical trial demonstrated that ALVAC prime/envelope protein boost vaccine regimen may represent a promising strategy for the development of an effective HIV-1 vaccine. Our earlier study demonstrated that a trimeric HIV-1 envelope gp145 from an Indian Glade C isolate elicited cross Glade neutralizing antibodies primarily towards Tier 1 isolates. In the present study, we examined the immunogenicity of DNA prime/envelope protein boost vaccine in rabbits using gp160 DNA of the Indian Glade C isolate with various cytoplasmic tail truncations and trimeric gp145 protein. Cytoplasmic tail mutants of gp160 exposed epitopes that reacted strongly with a number of broadly neutralizing human monoclonal antibodies against HIV-1. Overall, envelope specific titers were found to be similar in all rabbit groups with higher pseudovirus neutralization in protein only immunized rabbits. The complete linear epitope mapping of rabbit immune sera revealed strong binding to C1, C2, V3, C3 and C4 domains of gp145. Importantly, reactivity of gp41 ecto-domain peptides was observed in DNA prime/protein boost sera but not in the sera of rabbits immunized with protein alone. Moreover, membrane anchored but not soluble envelope encoding DNA immunization elicited antibodies against linear epitopes on the conserved gp41 ecto-domain. Together, these results suggest that priming with DNA encoding cytoplasmic domains of Env alters the quality of antibodies elicited following protein boost and hence may be utilized to generate protective immunity by HIV-1 vaccine. (C) 2016 Elsevier Ltd. All rights reserved.
机译：RV144人类临床试验的部分成功表明，ALVAC初免/包膜蛋白加强疫苗方案可能代表了开发有效HIV-1疫苗的有希望的策略。我们较早的研究表明，来自印度Glade C分离株的三聚体HIV-1包膜gp145引起交叉Glade中和抗体，主要针对第1层分离株。在本研究中，我们使用具有多种细胞质尾截短和三聚体gp145蛋白的Indian Glade C分离株的gp160 DNA检查了兔DNA初免/包膜蛋白加强疫苗的免疫原性。 gp160的细胞质尾突变体暴露出抗原决定簇，该抗原决定簇与许多广泛中和的针对HIV-1的人类单克隆抗体发生了强烈反应。总体而言，发现在所有兔组中，只有蛋白免疫的兔中包膜特异性滴度更高，假病毒中和度更高。兔免疫血清的完整线性表位作图揭示了与gp145的C1，C2，V3，C3和C4域的强结合。重要的是，在DNA初免/蛋白加强血清中观察到gp41胞外域肽的反应性，而在仅用蛋白免疫的兔子的血清中未观察到。而且，膜锚定但不可溶性的编码DNA免疫的包膜引发了针对保守的gp41胞外域上的线性表位的抗体。总之，这些结果表明，用编码Env胞质结构域的DNA进行引物可改变蛋白质增强后引发的抗体的质量，因此可被HIV-1疫苗用于产生保护性免疫。 （C）2016 Elsevier Ltd.保留所有权利。

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