Maruggi Giulietta, Chiarot Emiliano, Giovani Cinzia, Buccato Scilla, Bonacci Stefano, Frigimelica Elisabetta, Margarit Immaculada, Geall Andrew, Bensi Giuliano, Maione Domenico
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
Vaccine. 2017 Jan 5;35(2):361-368. doi: 10.1016/j.vaccine.2016.11.040. Epub 2016 Dec 7.
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.
核酸疫苗是一种颇具吸引力的疫苗接种方法，它结合了病毒载体疫苗和减毒活疫苗的优点，而没有每种技术的固有局限性。我们开发了一种新技术，即自我扩增mRNA（SAM）平台，该平台基于作为疫苗配制和递送的自我扩增mRNA的合成。SAM疫苗已被证明能在小动物和非人类灵长类动物中激发针对多种病毒抗原的强大先天性和适应性免疫反应，因此是一种针对病毒感染的安全且通用的工具。为了评估SAM技术是否可用于更广泛的靶点，我们研究了表达A组（GAS）和B组（GBS）链球菌抗原的SAM疫苗的免疫原性和效力，以此作为细菌病原体的模型。两种原型细菌抗原（双突变GAS链球菌溶血素O（SLOdm）和GBS菌毛2a主干蛋白（BP - 2a））通过SAM载体成功表达。用这两种疫苗免疫的小鼠产生了大量功能完全正常的血清抗体。SAM疫苗产生的抗体反应能够在GAS和GBS感染的小鼠模型中提供持续的保护。加入真核分泌信号或用重组蛋白加强免疫会导致更高的特异性抗体水平和保护作用。我们的结果支持了将SAM疫苗用作针对多种病毒和细菌病原体的潜在解决方案的概念，这归因于制造过程的通用性和所引发的广泛保护性免疫反应。
