<b>Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease</b>

The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV. We developed a SUDV vaccine candidate based on a nanocarrier (LION^TM) complexed with an alphavirus-based replicon RNA. Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection. Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses correlate with decreased virus replication and survival. This result warrants further studies in larger animal species to ensure that protective efficacy is maintained with the single-dose LION-SUDV vaccine.2022年与2025年乌干达暴发的苏丹病毒（SUDV）疫情，在乌干达国内及整个东非地区均引发了公共卫生层面的担忧。目前尚无针对SUDV的获批上市防治手段。我们研发了一款基于纳米载体（LION™）的SUDV候选疫苗，该载体与基于甲病毒的复制子RNA复合而成。本研究对比了两款LION-SUDV疫苗的保护效力：一款仅编码SUDV糖蛋白（GP），另一款则联合编码埃博拉病毒（EBOV）糖蛋白（GP，即LION-Combination疫苗）。同时我们纳入了对EBOV具有保护作用的LION-EBOV疫苗组，以探究其针对SUDV感染的交叉保护潜力。实验采用雌性豚鼠疾病模型，在以致死剂量豚鼠适应性SUDV攻毒前3周实施单剂量疫苗接种。研究结果显示，LION-SUDV与LION-Combination疫苗可实现100%的存活率与保护效果，而LION-EBOV疫苗的保护率仅为50%。抗原特异性体液免疫应答与病毒复制水平降低及存活率提升显著相关。上述研究结果表明，需在更大体型的动物物种中开展进一步研究，以验证单剂量LION-SUDV疫苗的保护效力能否得以维持。