Ulmer Jeffrey B, Mansoura Monique K, Geall Andrew J
Novartis Vaccines, Inc. , 350 Massachusetts Ave., Cambridge, MA 02139 , USA +1 617 871 3745 ;
Expert Opin Drug Discov. 2015 Feb;10(2):101-6. doi: 10.1517/17460441.2015.996128. Epub 2015 Jan 13.
Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria.
This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity.
The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.
自我扩增mRNA疫苗正作为一种平台技术进行研发，有潜力用于广泛的靶点。其制造的合成生产方法，结合生物信息学和合成生物学的现代工具，使这些疫苗能够从电子基因序列快速生产出来。到目前为止，在流感、呼吸道合胞病毒、狂犬病、埃博拉、巨细胞病毒、人类免疫缺陷病毒和疟疾方面已取得临床前概念验证。
本社论重点介绍了自我扩增mRNA疫苗发现和开发的关键里程碑，并回顾了它们如何用作快速反应平台。该论文指出RNA载体设计和非病毒递送方面未来的改进可能如何导致有效剂量降低和生产能力提高。
自我扩增mRNA疫苗非病毒递送的前景非常广阔。与其他类型的核酸疫苗一样，这些疫苗有可能借鉴减毒活疫苗的积极特性，同时消除许多潜在的安全限制。因此，这种方法可以实现按需生产疫苗的概念，作为对实际威胁的快速反应，而不是基于对可能威胁的流行病学预测来部署战略储备。
