Runge Solveig, Olbert Marita, Herden Christiane, Malberg Sara, Römer-Oberdörfer Angela, Staeheli Peter, Rubbenstroth Dennis
Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
Institute for Veterinary Pathology, University Justus Liebig Gießen, Frankfurter Str. 96, D-35392 Gießen, Germany.
Vaccine. 2017 Jan 23;35(4):557-563. doi: 10.1016/j.vaccine.2016.12.022. Epub 2016 Dec 22.
Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 10foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 10ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations.
禽博尔纳病毒是嗉囊扩张病（PDD）的病原体，PDD是一种慢性神经疾病，通常会导致包括濒危物种在内的鹦鹉类动物死亡。迄今为止，尚无有效的治疗方法或免疫预防措施。我们之前的研究表明，病毒载体疫苗可以延缓同源博尔纳病毒感染的病程，但在未能预防持续性感染的情况下，无法预防PDD。本研究的目的是优化我们的禽博尔纳病毒疫苗接种和感染模型，以更好地模拟自然博尔纳病毒感染，从而实现对异源攻击感染的全面保护。我们观察到，鹦鹉博尔纳病毒2型（PaBV-2）通过肌肉注射和皮下注射联合给药，每只鸟仅注射低至10个空斑形成单位（ffu），就能轻易感染鸡尾鹦鹉（Nymphicus hollandicus），而通过口服和眼鼻途径给予高500倍剂量的同一病毒，并不会导致持续性感染。这些结果表明，用该病毒进行实验性博尔纳病毒攻击感染应通过非肠道途径进行。用表达PaBV-4核蛋白和磷蛋白基因的新城疫病毒（NDV）和安卡拉痘苗病毒（MVA）载体对鸡尾鹦鹉进行初免-加强免疫，在用10ffu异源PaBV-2进行非肠道攻击感染后，可显著阻断博尔纳病毒的复制。在六只接种疫苗的鸟中，只有两只在少数器官中检测到极低的病毒水平。因此，只有一只接种疫苗的鸟出现了与轻度PDD相关的微观病变，而 mock-疫苗接种对照组则未受到PaBV-2感染和炎症的保护。我们的结果表明，NDV和MVA载体疫苗可以预防侵入性异源博尔纳病毒攻击感染和随后的PDD。这些载体疫苗是在鹦鹉种群中对抗禽博尔纳病毒的一种有前途的工具。
