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）作为宿主免疫的递送载体，以螺旋体抗原作为疫苗靶点。我们将评估对ndv免疫的啮齿动物宿主对伯氏疏螺旋体感染的保护作用，即莱姆病或莱姆博氏疏螺旋体病。新城疫病毒是一种禽病毒，在包括灵长类动物在内的哺乳动物中具有高度免疫原性，但已减毒。NDV是一种安全的人用疫苗载体，临床试验研究表明，抗NDV抗体很容易在人体内诱导产生。通过反向遗传学可以很容易地从转染的cdna中产生传染性NDV，这种方法对研究病毒的基本生物学和发病机制很有帮助。近年来，这些技术也被用于具有转译目的的研究，例如设计针对各种动物和人类疾病的NDV载体。在本文中，我们将评估ndv衍生载体是否可以作为宿主免疫伯氏疏螺旋体感染的另一种方法，并确定几种新鉴定的新型螺旋体抗原的保护效果。我们目前的数据表明，即使用重组NDV对啮齿动物进行单次免疫，也会引起针对所检测的螺旋体抗原的强大抗体反应。我们将启动携带几种新靶抗原的NDV构建体的其他系列免疫研究，评估啮齿动物宿主的抗体发展，并最终确定宿主中的特异性抗体是否干扰螺旋体的传染性。如果不止一种抗原是有希望的，我们将结合多种抗原来寻找加性效应。我们也将进行研究

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.