接受基孔肯雅病毒樣顆粒疫苗（Vimkunya）受試者的血清被動轉(zhuǎn)移可完全保護非人靈長類動物免受病毒血癥感染
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是一種寨卡病毒（CHIKV）病毒樣顆粒（VLP）疫苗，對≥12歲人群安全性良好，可誘導快速持久的血清中和抗體（SNA）反應(yīng)。本研究評估了人源CHIKV VLP抗血清對 cynomolgus macaques（食蟹獼猴）異源CHIKV攻擊的保護效力，并確定了可完全阻斷病毒血癥的SNA滴度。接受陰性對照血清的獼猴出現(xiàn)可檢測的病毒血癥和RNAemia，而接受對照抗CHIKV IgG或預(yù)攻擊NT80≥25.7的CHIKV VLP抗血清的獼猴在攻擊后10天內(nèi)未檢測到病毒血癥/RNAemia。邏輯回歸分析顯示，預(yù)攻擊NT80值為23.6和25.9時分別對應(yīng)80%和90%的保護概率。血清流行病學研究數(shù)據(jù)表明，中和滴度>1:10可為康復期患者提供保護。美國和歐洲監(jiān)管機構(gòu)選定的SNA NT80閾值為100，用于預(yù)測人類對CHIKV疾病的保護效力，該閾值較實際保守約4倍。
