Immune inductor and effector sites in the upper airways of cattle and influence of site of antigen expression on induction of mucosal immunity

许多导致牛患病的微生物通过侵入呼吸道进入动物体内。以这种方式入侵牛的一些微生物对动物福利构成了重大威胁，并造成了严重的经济损失。例子包括引起牛结核病的细菌--牛分枝杆菌，以及引起口蹄疫的病毒。尽管已经有了针对许多此类微生物的疫苗，但许多只有部分有效。部分原因可能是它们未能在呼吸道分泌物中诱导抗体，阻止微生物附着和定植呼吸道内的细胞，或穿透和在这些细胞内复制。因此，显然有必要开发更有效的疫苗，在牛的上呼吸道诱导保护性免疫。越来越多的证据表明，在呼吸道内获得保护方面，经鼻接种疫苗优于在其他地点接种疫苗。然而，事实证明，安全有效的鼻腔疫苗很难开发。这个项目的目的是更详细地了解牛的上呼吸道对感染做出反应并产生保护性免疫反应的方式。这将通过在实验室研究表达外源基因并感染牛呼吸道而不会导致疾病的活病毒、从牛的上呼吸道不同区域获得的牛呼吸道细胞培养和免疫系统细胞的相互作用来实现。这些实验室研究的结果将与经鼻注射病毒给牛犊后引起的免疫反应进行比较。该项目产生的信息将有助于设计有效的鼻腔疫苗，以保护牛免受一些重要的传染病，如口蹄疫和牛结核病的侵袭。此外，这些研究可能导致开发测试新的鼻用疫苗的实验室方法，从而减少研究中使用的动物数量。

Many micro-organisms that cause disease in cattle enter the animal's body by invading the respiratory tract. A number of micro-organisms which invade cattle in this way are a significant threat to animal welfare and cause severe economic loss. Examples include the bacteria, Mycobacterium bovis, which causes bovine tuberculosis, and the virus that causes foot and mouth disease. Although vaccines to a number of such micro-organisms are available, many are only partially effective. This may be partly due to their failure to induce antibodies in respiratory secretions that prevent the micro-organisms from attaching to and colonising the cells lining the respiratory tract or from penetrating and replicating within these cells. There is therefore a clear need to develop more effective vaccines that induce protective immunity in the upper airways of cattle. There is increasing evidence that nasal delivery of vaccines is superior to vaccination at other sites in eliciting protection within the respiratory tract. However, safe and effective nasal vaccines have proved difficult to develop. The purpose of this project is to gain a more detailed understanding of the ways in which the upper airways of cattle respond to infection and mount a protective immune response. This will be achieved by studying in the laboratory the interactions of a live virus that expresses foreign genes and infects the bovine respiratory tract without causing disease, cultures of bovine airway cells and cells of the immune system that have been obtained from different regions of the upper airways of cattle. The findings from these laboratory studies will be compared with immune responses induced after nasal delivery of the viruses to calves. The information generated from this project will aid the design of effective nasal vaccines to protect cattle against a number of important infectious diseases such as foot and mouth disease and bovine tuberculosis. In addition, these studies may lead to the development of laboratory methods for testing new nasal vaccines, thereby reducing the number of animals used in research.