研究递送系统设计对自扩增RNA疫苗效力的影响。

Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines.

作者信息

Anderluzzi Giulia, Lou Gustavo, Gallorini Simona, Brazzoli Michela, Johnson Russell, O'Hagan Derek T, Baudner Barbara C, Perrie Yvonne

机构信息

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 ORE, Scotland, UK.

GSK, 53100 Siena 1, Italy.

出版信息

Vaccines (Basel). 2020 May 8;8(2):212. doi: 10.3390/vaccines8020212.

messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.

基于信使核糖核酸（mRNA）的疫苗兼具减毒活疫苗和亚单位疫苗的优点。为了将其应用于临床，需要与递送系统一起配制。然而，比较不同递送平台的体内研究有限。因此，我们比较了四种不同的阳离子平台：（1）脂质体，（2）固体脂质纳米颗粒（SLN），（3）聚合物纳米颗粒（NP）和（4）乳剂，以递送一种自我扩增mRNA（SAM）疫苗。所有制剂均含有不可电离的阳离子脂质1,2-二油酰基-3-三甲基铵丙烷（DOTAP）或二甲基二辛基溴化铵（DDA），并根据物理化学特性、体外转染效率和体内疫苗效力进行了表征。我们的结果表明，包裹SAM的DOTAP聚合物纳米颗粒、DOTAP脂质体和DDA脂质体在体外诱导了最高的抗原表达，其中，DOTAP聚合物纳米颗粒在体内候选物中触发体液免疫和细胞免疫方面最为有效。