Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD
Clinical Protection of Goats against CpHV-1 Induced Genital Disease with a BoHV-4-Based Vector Expressing CpHV-1 gD
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DOI：
10.1371/journal.pone.0052758
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发表时间：
2013-01-03
期刊：
影响因子：
3.7
通讯作者：
Tempesta, Maria
中科院分区：
文献类型：
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作者：
Donofrio, Gaetano;Franceschi, Valentina;Tempesta, Maria
山羊疱疹病毒1型（Caprine herpesvirus type 1，CpHV-1）是一种α疱疹病毒，可引起妊娠山羊流产和羔羊全身性疾病，发病率和死亡率高。此外，山羊疱疹病毒1型感染代表了人类疱疹病毒诱导的生殖器疾病的有价值的大型动物模型，可用于病原学研究、新疫苗和抗病毒分子测试。在此，构建了基于牛疱疹病毒4型（BoHV-4）的载体，该载体来源于BoHV-4的无致病性分离株并表达免疫显性CpHV-1糖蛋白D（BoHV-4-A-gD（cp）gD（106 Delta）TK），并评价了其保护山羊免受CpHV-1诱导的生殖器疾病的能力。首先通过体内图像分析在体内/离体测试重组BoHV-4施用的皮下途径，并通过山羊皮肤原代培养物制备和转导在体外测试重组BoHV-4施用的皮下途径。接下来，用两种重组BoHV 4、BoHV-4-A-gD（cp）gD（106）Delta TK或BoHV-4-CMV-IgK-gE 2gD-TM在山羊中进行探索性免疫和安全性研究。在这两种情况下，均无明显临床体征，但在所有接种动物中均产生了良好滴度的血清中和抗体。当使用高致病性剂量的CpHV-1在一组新动物中进行攻毒实验时，所有接种BoHV-4-AgD（cp）gD（106）Delta TK的山羊相对于未接种对照组均受到保护，免于CpHV-1诱导的生殖器疾病，未接种对照组显示出具有高临床评分的典型阴道病变以及持久的病毒脱落。综上所述，本研究中获得的数据验证了基于BoHV-4的载体作为山羊疫苗接种针对CpHV-1诱导的生殖器疾病的安全有效的病毒载体，并为进一步的应用铺平了道路。
Caprine herpesvirus type 1 (CpHV-1) is an alphaherpesvirus causing genital disease leading to abortion in adult pregnant goats and a systemic disease with high morbility and mortality in kids. Further, Caprine herpesvirus 1 infection represents a valuable large animal model for human herpesvirus induced genital disease, exploitable for pathogenic studies, new vaccines and antiviral molecules testing. Here, the bovine herpesvirus 4 (BoHV-4) based vector derived from an apathogenic isolate of BoHV-4 and expressing the immunodominant CpHV-1 glycoprotein D (BoHV-4-A-gD(cp)gD(106 Delta)TK) was constructed and its ability to protect goats against CpHV-1 induced genital disease evaluated. The subcutaneous route of recombinant BoHV-4 administration was first tested in vivo/ex vivo by in vivo image analysis and in vitro by goat skin primary cultures preparation and transduction. Next, an exploratory immunization and safety study in goats was performed with two recombinant BoHV4, BoHV-4-A-gD(cp)gD(106)Delta TK or BoHV-4-CMV-IgK-gE2gD-TM. In both cases no clinical signs were evident but a good titer of serum neutralizing antibodies was produced in all inoculated animals. When a challenge experiment was performed in a new group of animals using a highly pathogenic dose of CpHV-1, all the vaccinated goats with BoHV-4-AgD(cp)gD(106)Delta TK were protected toward CpHV-1 induced genital disease respect to the unvaccinated control which showed typical vaginal lesions with a high grade of clinical score as well as a long lasting viral shedding. In summary, the data acquired in the present study validate BoHV-4-based vector as a safe and effective viral vector for goat vaccination against CpHV-1 induced genital disease and pave the way for further applications.