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A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs
npj Vaccines ( IF 6.9 ) Pub Date : 2019-02-08 , DOI: 10.1038/s41541-019-0104-x
Derek R. Stein , Bryce M. Warner , Geoff Soule , Kevin Tierney , Kathy L. Frost , Stephanie Booth , David Safronetz

The World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates.



中文翻译:

基于重组水疱性口炎的拉沙热疫苗可对豚鼠产生快速和长期的保护,使其免受致命的拉沙病毒感染

世界卫生组织已将拉沙病毒(LASV)确定为在不久的将来引起严重爆发的五种病原体之一。这项研究评估了领先的候选疫苗表达LASV糖蛋白(VSVΔG/ LASVGPC)的重组水泡性口腔炎病毒的能力,以及诱导对适应豚鼠致命LASV(GPA-LASV)的快速和长期免疫的能力。在疫苗接种后第7、14、25、189和355天,对单亲VSVΔG/ LASVGPC的近交豚鼠进行致命疫苗接种,然后进行致命性GPA-LASV攻击。接种后第7天和第14天在所有时间点均达到了统计上显着的快速和长期保护,且100%达到了保护。接种后25天和6个月分别达到83%和87%的保护率。接种疫苗一年后,对豚鼠进行攻击时,可获得71%的保护。从一些但不是全部动物的血清和组织中分离出了明显的传染性病毒。还每月检测导致LASV攻击的总LASVGPC特异性IgG滴度,但是,尚不清楚单独的抗体是否与短期和长期生存相关。这些研究证实,在积极的近交感染模型中,单剂VSVΔG/ LASVGPC可以诱导对LASV感染的快速和长期保护,并支持非人类灵长类动物的进一步发展。尚不清楚单独的抗体是否与短期和长期生存相关。这些研究证实,在积极的近交感染模型中,单剂VSVΔG/ LASVGPC可以诱导对LASV感染的快速和长期保护,并支持非人类灵长类动物的进一步发展。尚不清楚单独的抗体是否与短期和长期生存相关。这些研究证实,在积极的近交感染模型中,单剂VSVΔG/ LASVGPC可以诱导对LASV感染的快速和长期保护,并支持非人类灵长类动物的进一步发展。

更新日期:2019-11-18
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