NDV-vectored Lyme disease vaccines

描述(由申请人提供)：我们建议评估新城疫病毒(NDV)作为以疏螺旋体抗原为疫苗靶标的宿主免疫的传递载体的使用。我们将评估新城疫免疫啮齿动物宿主对伯氏疏螺旋体感染的保护作用，这种疾病被称为莱姆病或莱姆疏螺旋体病。新城疫病毒是一种高度免疫原性的禽类病毒，但在包括灵长类在内的哺乳动物中减弱。新城疫病毒是人类使用的一种安全的疫苗载体，临床试验研究表明，抗新城疫病毒抗体很容易在人体内诱导产生。利用反向遗传学的方法，可以很容易地从转基因的新城疫病毒中产生传染性新城疫病毒，这一方法对于研究新城疫病毒的基础生物学和致病机制具有重要意义。近年来，这些技术也被用于具有翻译目标的研究，例如设计针对各种动物和人类疾病的新城疫病毒载体。在这项建议中，我们将评估新城疫病毒衍生载体是否可以作为宿主免疫伯氏杆菌感染的另一种方法，并确定几种新鉴定的螺旋体抗原的保护效果。我们目前的数据表明，即使用重组新城疫病毒对啮齿动物进行一次免疫，也能引起对所测试的疏螺旋体抗原的强大抗体反应。我们将用携带几个新的靶抗原的新城疫病毒构建物启动额外的一系列免疫研究，评估啮齿动物宿主中的抗体发展，并最终确定宿主中的特定抗体是否干扰螺旋体的传染性。如果不止一个抗原是有希望的，我们将结合多个抗原来寻找相加效应。我们还将进行研究，以 了解与宿主保护相关的体液和细胞免疫反应的机制。总体而言，这些研究将有助于制定预防伯氏杆菌引起的多器官感染的措施。

DESCRIPTION (provided by applicant): We propose to evaluate the use of the Newcastle disease virus (NDV) as a delivery vector for host immunization with borrelial antigens as vaccine targets. We will assess protection of NDV-immunized rodent hosts against Borrelia burgdorferi infection, known as Lyme disease or Lyme borreliosis. NDV is an avian virus that is highly immunogenic yet attenuated in mammals including primates. NDV is a safe vaccine vector for human use and anti-NDV antibodies are readily induced in human, as shown in clinical trial studies. Infectious NDV can be easily produced from transfected cDNAs by reverse genetics, a method that has been instrumental for studying basic biology and pathogenesis of the virus. In recent years, these technologies are also adopted for studies with translational goals, such as engineering NDV vectors against variety of animal and human diseases. In this proposal, we will assess if NDV-derived vectors could be an additional approach for host immunization against B. burgdorferi infection and identify protective efficacy of several newly characterized novel spirochete antigens. Our current data show that even a single immunization of rodents with recombinant NDV elicits a robust antibody response against tested borrelial antigens. We will initiate additional series of immunization studies with NDV constructs carrying several new target antigens, assess antibody development in rodent hosts and finally determine if specific antibodies in the host interfere with spirochete infectivity. If more than one antigen is promising we will combine multiple antigens in search of an additive effect. We will also perform studies for understanding the mechanism of humoral and cellular immune responses associated with host protection. Overall, these studies will contribute to the development of preventive measures against multi-organ infection caused by B. burgdorferi.