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首页> 外文期刊>Vaccine >Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens
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Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens

机译：通过编码细菌抗原的自我扩增mRNA疫苗诱导的免疫原性和保护疗效

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Nucleic acid vaccines represent an attractive approach to vaccination, combining the positive attributes of both viral vectors and live-attenuated vaccines, without the inherent limitations of each technology. We have developed a novel technology, the Self-Amplifying mRNA (SAM) platform, which is based on the synthesis of self-amplifying mRNA formulated and delivered as a vaccine. SAM vaccines have been shown to stimulate robust innate and adaptive immune responses in small animals and non-human primates against a variety of viral antigens, thus representing a safe and versatile tool against viral infections. To assess whether the SAM technology could be used for a broader range of targets, we investigated the immunogenicity and efficacy of SAM vaccines expressing antigens from Group A (GAS) and Group B (GBS) Streptococci, as models of bacterial pathogens. Two prototype bacterial antigens (the double-mutated GAS Streptolysin-O (SLOdm) and the GBS pilus 2a backbone protein (BP-2a)) were successfully expressed by SAM vectors. Mice immunized with both vaccines produced significant amounts of fully functional serum antibodies. The antibody responses generated by SAM vaccines were capable of conferring consistent protection in murine models of GAS and GBS infections. Inclusion of a eukaryotic secretion signal or boosting with the recombinant protein resulted in higher specific antibody levels and protection. Our results support the concept of using SAM vaccines as potential solution for a wide range of both viral and bacterial pathogens, due to the versatility of the manufacturing processes and the broad spectrum of elicited protective immune response. (C) 2016 GSK Vaccines. Published by Elsevier Ltd.
机译：核酸疫苗代表一种有吸引力的疫苗接种方法，组合病毒载体和活病毒疫苗的阳性属性，而无需每种技术的固有局限性。我们开发了一种新颖的技术，自增压mRNA（SAM）平台，基于配制和递送作为疫苗的自增强mRNA的合成。已显示SAM疫苗以刺激小型动物和非人类原始的鲁棒天生和适应性免疫应答，其针对各种病毒抗原，因此代表一种安全和通用的病毒感染工具。为了评估SAM技术是否可用于更广泛的靶标，我们研究了SAM疫苗表达来自A（气体）和B组（GBS）链球菌的抗原的抗原的免疫原性和功效，作为细菌病原体的模型。由SAM载体成功地表达了两个原型细菌抗原（双突变的气体链霉素-O（SLODM）和GBS pilus 2a骨架蛋白（BP-2A））。用疫苗免疫的小鼠产生了大量的全功能性血清抗体。 SAM疫苗产生的抗体应答能够在尿嘧啶模型和GBS感染中赋予一致的保护。用重组蛋白包含真核分泌信号或升压导致更高的特异性抗体水平和保护。我们的结果支持使用SAM疫苗作为各种病毒和细菌病原体的潜在解决方案的概念，这是由于制造过程的多功能性和引发的保护性免疫应答的广谱。 （c）2016 GSK疫苗。 elsevier有限公司出版

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