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

页码：2782 / 2793

页数：12

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