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

动物疾病的日益增多使人们把注意力集中在基于免疫的疾病保护方法上。疫苗是指导免疫系统改善疾病保护的一种众所周知的方法，但它们不适用于某些疾病，并且在需要立即产生保护效果时（例如面对疾病暴发时）不有效。因此，需要其他策略来诱导保护性免疫。“第一反应者”或免疫系统的先天成分通过识别感染性有机体的特征作为“危险”信号来检测感染。这很快就会引发一种能够限制各种感染的反应（不像疫苗那样只能预防它们所针对的疾病）。这些危险信号之一是细菌DNA的一种模式特征，被称为CpG基序。这种模式可以在被称为寡核苷酸（ODN）的DNA小片段中合成，这种DNA小片段适合给动物服用。拟议的研究计划将确定CpG-ODN是否能刺激鸡对病毒感染的保护性免疫反应。我会在雏鸡还在蛋里的时候给它们注射CpG ODN，从而避免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，比如启动对免疫反应协调很重要的基因，以及产生抗病毒活性等功能。我打算证明，将CpG-ODN递送到呼吸道或胃肠道，这是大多数情况下感染的部位，将刺激保护性免疫反应。在此之前，我已经证明了CpG-ODN对新生鸡和成年鸡致命细菌感染的显著保护作用，并提出了研究计划，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，因此该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.