Live-attenuated RNA hybrid vaccine technology provides single-dose protection against Chikungunya virus

被引：13
作者：
Voigt, Emily A. [1 ]
Fuerte-Stone, Jasmine [1 ]
Granger, Brian [1 ]
Archer, Jacob [1 ]
Van Hoeven, Neal [1 ,2 ]
机构：
[1] Infect Dis Res Inst, 1616 Eastlake Ave East,Suite 400, Seattle, WA 98102 USA
[2] PAI Life Sci, 1616 Eastlake Ave East, Seattle, WA 98102 USA
来源：
MOLECULAR THERAPY | 2021年 / 29卷 / 09期
基金：
美国国家卫生研究院;
关键词：
YELLOW-FEVER; IMMUNOGENICITY; CHALLENGES; DELIVERY; IMMUNITY; STRAIN; SAFETY;
D O I：
10.1016/j.ymthe.2021.05.018
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
We present a live-attenuated RNA hybrid vaccine technology that uses an RNA vaccine delivery vehicle to deliver in vitro -transcribed, full-length, live-attenuated viral genomes to the site of vaccination. This technology allows ready manufacturing in a cell-free environment, regardless of viral attenuation level, and it promises to avoid many safety and manufacturing challenges of traditional live-attenuated vaccines. We demonstrate this technology through development and testing of a live -attenuated RNA hybrid vaccine against Chikungunya virus (CHIKV), comprised of an in vitro-transcribed, highly attenuated CHIKV genome delivered by a highly stable nanostructured lipid carrier (NLC) formulation as an intramuscular injection. We demonstrate that single-dose immunization of immunocompetent C57BL/6 mice results in induction of high CHIKV-neutralizing antibody titers and protection against mortality and footpad swelling after lethal CHIKV challenge.
引用
收藏
页码：2782 / 2793
页数：12
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