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

被引：41
作者：
Anderluzzi, Giulia [1 ,2 ]
Lou, Gustavo [1 ,2 ]
Gallorini, Simona [2 ]
Brazzoli, Michela [2 ]
Johnson, Russell [3 ]
O'Hagan, Derek T. [3 ]
Baudner, Barbara C. [2 ]
Perrie, Yvonne [1 ]
机构：
[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland
[2] GSK, I-53100 Siena 1, Italy
[3] GSK, Rockville, MD USA
来源：
VACCINES | 2020年 / 8卷 / 02期
基金：
欧盟地平线“2020”;
关键词：
self-amplifying RNA; liposomes; polymeric nanoparticles; solid lipid nanoparticles; emulsions; antigen expression; immunogenicity; SOLID-LIPID NANOPARTICLES; GENE-THERAPY; ADJUVANT FORMULATIONS; PROTECTIVE EFFICACY; NONVIRAL DELIVERY; IMMUNE-RESPONSES; DNA VACCINATION; SIRNA DELIVERY; PLASMID DNA; LIPOSOMES;
D O I：
10.3390/vaccines8020212
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
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页数：22
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