接受基孔肯雅病毒样颗粒疫苗（Vimkunya）受试者的血清被动转移可完全保护非人灵长类动物免受病毒血症感染
Passive transfer of human sera from chikungunya virus virus-like particle vaccine (Vimkunya) recipients fully protects non-human primates from viremia
Abstract
Vimkunya, a chikungunya virus (CHIKV) virus-like particle (VLP) vaccine, is well-tolerated and induces a rapid, durable serum neutralizing antibody (SNA) response in individuals aged ≥12 years. This study evaluated the efficacy of human CHIKV VLP antisera to protect cynomolgus macaques from heterologous CHIKV challenge and determined an SNA titer that confers complete protection against viremia. Macaques receiving negative control sera had detectable viremia and RNAemia, whereas those receiving control anti-CHIKV IgG or CHIKV VLP antisera with pre-challenge NT80 ≥ 25.7 had no detectable viremia/RNAemia through 10 days post-challenge. Logistic regression showed that pre-challenge NT80s of 23.6 and 25.9 corresponded with 80% and 90% probability of protection, respectively. Data from seroepidemiology studies demonstrated that a neutralizing titer of >1:10 is protective in convalescent persons. The SNA NT80 threshold of 100 selected by US and European regulators to predict protection against CHIKV disease in humans is conservative by a factor of ~4.
摘要
Vimkunya是一种寨卡病毒（CHIKV）病毒样颗粒（VLP）疫苗，对≥12岁人群安全性良好，可诱导快速持久的血清中和抗体（SNA）反应。本研究评估了人源CHIKV VLP抗血清对 cynomolgus macaques（食蟹猕猴）异源CHIKV攻击的保护效力，并确定了可完全阻断病毒血症的SNA滴度。接受阴性对照血清的猕猴出现可检测的病毒血症和RNAemia，而接受对照抗CHIKV IgG或预攻击NT80≥25.7的CHIKV VLP抗血清的猕猴在攻击后10天内未检测到病毒血症/RNAemia。逻辑回归分析显示，预攻击NT80值为23.6和25.9时分别对应80%和90%的保护概率。血清流行病学研究数据表明，中和滴度>1:10可为康复期患者提供保护。美国和欧洲监管机构选定的SNA NT80阈值为100，用于预测人类对CHIKV疾病的保护效力，该阈值较实际保守约4倍。
