Delivery of CpG-ODN against viral infections in chickens as an immunostimulant and vaccine adjuvant

动物疾病的日益增加使人们关注基于免疫的疾病保护方法。 疫苗是一种众所周知的指导免疫系统以改善疾病保护的方法，但它们对某些疾病不可用，并且当需要立即保护作用时无效，例如，面对疾病的爆发 因此，需要替代策略来诱导保护性免疫。 免疫系统的“第一反应者”或先天性组成部分通过将感染性生物体的特征识别为“危险”信号来检测感染。 这会迅速引发一种能够限制各种感染的反应（不像疫苗只针对它们所开发的疾病）。 这些危险信号之一是细菌DNA的特征模式，称为CpG基序。 这种模式可以在称为寡核苷酸（ODN）的小片段DNA中合成，其适合于施用给动物。 拟议的研究计划将确定CpG-ODN是否可以刺激鸡对病毒感染的保护性免疫反应。我会在小鸡还在蛋里的时候给它们注射CpG ODN，这样就避免了其他环境刺激对免疫系统的复杂影响。 我将寻找先天免疫激活的证据，例如开启对免疫反应协调重要的基因，以及产生抗病毒活性等功能。我打算证明，CpG-ODN的交付呼吸道或胃肠道，这是在大多数情况下感染的网站，将刺激保护性免疫反应。在此之前，我已经证明了CpG-ODN对新生和成年鸡的致死性细菌感染具有显著的保护作用，并且拟议的研究计划将探索CpG-ODN对鸡病毒感染的免疫刺激作用。由于许多先天免疫反应在各种物种中是相似的，因此结果不仅对家禽具有重要意义，而且也适用于兽医和人类医学的其他领域。

An increasing emergence of diseases in animals has focused attention on immune based methods of disease protection. Vaccines are a well known method to direct the immune system for improved disease protection, but they are not available for some diseases and are not effective when an immediate protective effect is required, e.g., in the face of an disease outbreak. Therefore, alternate strategies to induce protective immunity are required. The "first responder" or innate component of the immune system detects infection by recognizing features characteristic of infectious organisms as "danger" signals. This quickly triggers a response capable of limiting a variety of infections (unlike vaccines which protect only against the disease for which they were developed). One of these danger signals is a pattern characteristic of bacterial DNA, known as CpG motifs. This pattern can be synthesized in small pieces of DNA known as oligonucleotides (ODN), which are suitable for administration to animals. The proposed research program will determine if CpG-ODN can stimulate protective immune responses against viral infections in chickens. I will administer CpG ODN to chicks while still in the egg, thus avoiding the complicating effects of other environmental stimuli on the immune system. I will look for evidence of activation of innate immunity, such as the turning on genes important for immune response coordination, and functions such as production of antiviral activity. I intend to demonstrate that delivery of CpG-ODN to the respiratory or gastrointestinal tracts, which are the sites of infection in most cases, will stimulate protective immune responses. Previously, I have demonstrated a significant protective effect of CpG-ODN against lethal bacterial infections in neonatal and adult chickens, and proposed research program will explore immunostimulatory effect of CpG-ODN against viral infections in chickens. Since many innate immune responses are similar in a variety of species, the results are significant not only for poultry, but are also applicable in other areas of veterinary and human medicine.