Rapid protection induced by a single-shot Lassa vaccine in cynomolgus monkeys

Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine. 3 groups of 3 animals ; 4 to 6 timepoints by animals

拉沙热（Lassa fever）疫情每年都会波及西非国家，目前尚无获批上市的疫苗可减轻这种病毒性出血热的疾病负担。我们此前研发了MeV-NP单剂疫苗，该疫苗可在拉斯萨病毒（Lassa virus）感染前1个月或1年以上的食蟹猴（cynomolgus monkeys）体内诱导保护性免疫，且能够抵御异源毒株。鉴于疫情期间拉斯萨病毒的传播范围有限，且医院内传播（nosocomial transmission）风险极高，在未开展预防性疫苗接种的疫情期间，能够快速诱导保护作用的疫苗可用于保护暴露人群。我们通过在单次接种MeV-NP后16天或8天，对已具备MeV预存免疫的食蟹猴开展攻毒试验，探究免疫后保护性免疫诱导所需时长能否缩短。所有免疫食蟹猴均未发病，并快速抑制了病毒复制。其中，攻毒前8天接种的受试动物展现出最优的病毒复制控制效果，可针对病毒糖蛋白（viral glycoprotein）引发强烈的CD8 T细胞（CD8 T-cell）应答。另有一组受试动物在攻毒后1小时接种了疫苗，该组动物未产生任何保护性免疫应答，且与对照组动物一样出现致死性病症。本研究证实，在已存在MeV预存免疫的情况下，MeV-NP可诱导针对拉沙热的快速保护性免疫应答，但该疫苗大概率无法用作治疗性疫苗（therapeutic vaccine）。实验分为3组，每组3只受试动物；每只动物设置4至6个采样时间点。