Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
Virology. 2019 May;531:219-232. doi: 10.1016/j.virol.2019.03.014. Epub 2019 Mar 22.
Equid herpesvirus-1 (EHV-1) outbreaks continue despite widely used vaccination. We demonstrated previously that an ORF1/ORF71 gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) is less virulent than its parent Ab4 virus. Here, we describe the Ab4 challenge infection evaluating protection induced by the Ab4ΔORF1/71 vaccine candidate. Susceptible control horses developed respiratory disease, fever, nasal shedding, and viremia. Full protection after challenge infection was observed in 5/5 previously Ab4 infected horses and 3/5 Ab4ΔORF1/71 horses. Two Ab4ΔORF1/71 horses developed short-lasting viremia and/or virus shedding. Protective immunity in the respiratory tract was characterized by pre-existing EHV-1-specific IgG4/7 antibodies, the absence of IFN-α secretion and rapidly increasing IgG4/7 upon challenge infection. Pre-existing systemic EHV-1-specific IgG4/7 highly correlated with protection. T-cell immunity was overall low. In conclusion, protective immunity against EHV-1 infection including prevention of viremia was associated with robust systemic and intranasal IgG4/7 antibodies suggesting immediate virus neutralization at the local site.
尽管广泛使用疫苗，但马疱疹病毒 1 型（EHV-1）爆发仍在继续。我们之前证明，EHV-1 株 Ab4 的 ORF1/ORF71 基因缺失突变体比其亲本 Ab4 病毒的毒力更低。在这里，我们描述了 Ab4 攻毒感染，评估了 Ab4ΔORF1/71 疫苗候选物诱导的保护作用。易感对照马出现呼吸疾病、发热、鼻分泌物和病毒血症。在 5/5 只先前感染 Ab4 的马和 3/5 只 Ab4ΔORF1/71 马中观察到完全保护免受攻毒感染。2 只 Ab4ΔORF1/71 马出现短暂的病毒血症和/或病毒脱落。呼吸道中的保护性免疫特征是预先存在的 EHV-1 特异性 IgG4/7 抗体、缺乏 IFN-α 分泌以及在攻毒感染时迅速增加的 IgG4/7。预先存在的全身性 EHV-1 特异性 IgG4/7 与保护高度相关。T 细胞免疫总体较低。总之，针对 EHV-1 感染的保护性免疫包括预防病毒血症与强大的全身性和鼻内 IgG4/7 抗体相关，表明在局部立即中和病毒。
