<b>Single-dose VSV-Sudan virus vaccine protects macaques from lethal Sudan virus infection within one week</b>

Uganda’s most recent Sudan virus (SUDV) outbreak created a public health emergency in Uganda and the Eastern Africa region. Currently, there are licensed countermeasures for Ebola virus (EBOV); however, there are no licensed vaccines or therapeutics against SUDV.We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein as the viral antigen. Cynomolgus macaques were vaccinated with a single intramuscular (IM) dose of VSV-SUDV either one month or one week prior to SUDV challenge. A third group was vaccinated with a single IM dose of VSV-EBOV one month prior to SUDV challenge to assess its cross-protective potential since SUDV and EBOV are related filoviruses. All vaccinated nonhuman primates (NHPs) developed antigen-specific IgG within 2 weeks of vaccination, including cross-reactive responses as demonstrated by ELISA. After IM challenge with a lethal dose of SUDV, all VSV-SUDV-vaccinated NHPs were uniformly protected from disease. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between day 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high titer viremia, high viral organ load, dysregulated cytokine profiles and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV one month before challenge resulted in a profound and sustained antibody response with a diverse functionality profile which was not observed to the same extend in NHPs vaccinated one week before challenge.Taken together, we demonstrated that VSV-EBOV provided no relevant protection against SUDV infection in NHPs highlighting the need for species-specific vaccines against filoviruses. Furthermore, our data show that VSV-SUDV is a fast-acting single-dose vaccine ideal for use in future outbreaks.乌干达近期暴发的苏丹病毒（SUDV）疫情，在乌干达及东非地区引发公共卫生紧急事件。目前已有获批的埃博拉病毒（EBOV）防控对策，但尚无针对SUDV的获批疫苗或治疗药物。 我们开发了一款以水疱性口炎病毒（VSV）为载体、表达SUDV糖蛋白作为病毒抗原的疫苗。将食蟹猕猴分别于SUDV攻毒前1个月或1周，通过肌内注射（IM）接种单剂VSV-SUDV疫苗；另有一组于攻毒前1个月接种单剂VSV-EBOV疫苗，以评估其交叉保护潜力——因SUDV与EBOV均属于丝状病毒。 所有接种疫苗的非人灵长类动物（NHPs）均在接种后2周内产生抗原特异性IgG抗体，酶联免疫吸附试验（ELISA）证实其中存在交叉反应性应答。 在以致死剂量SUDV进行肌内攻毒后，所有接种VSV-SUDV的NHPs均获得完全的疾病保护。与之相反，接种VSV-EBOV的实验组与对照组动物均在攻毒后第5至7天发病死亡，表现出典型的苏丹病毒病症状，伴随高滴度病毒血症、高病毒组织载量、细胞因子谱失调及典型病理变化。 于攻毒前1个月接种VSV-SUDV的NHPs，其体液免疫应答可产生强烈且持久的抗体反应，且具备多样化的功能特征；这一效果在攻毒前1周接种的动物中未达到同等程度。 综上，我们证实VSV-EBOV无法为NHPs提供针对SUDV感染的有效保护，凸显了开发针对丝状病毒的物种特异性疫苗的必要性。此外，本研究数据表明，VSV-SUDV是一款起效迅速的单剂疫苗，非常适用于未来的疫情防控。