C DIFFICILE ARU AS A CARRIER PROTEIN IN VACCINES

即使疫苗接种项目取得了许多进展，但传染性 疾病继续给卫生职业带来严重问题。在……里面 工业化国家，梭状芽胞杆菌等机会性病原体 艰难梭菌和金黄色葡萄球菌继续导致疾病 住院病人。婴幼儿因流行性感冒引起的感染 嗜血杆菌、链球菌和奈瑟氏菌仍然是一种严重的健康问题 威胁。在较贫穷的国家，估计有10人死于肠道感染 到每年1200万人，其中大多数是一岁以下的人。 因此，继续开发新的方法是很重要的 疫苗。约翰·罗宾斯博士和瑞秋博士的研究结果 施尼尔森在国家儿童健康和人类发展研究所 研究表明，由结合在一起的胶囊多糖组成的疫苗 载体毒素，如破伤风、白喉毒素和假单胞菌外毒素 是非常有效的。根据这些研究结果，我们建议评估 无毒重组艰难梭菌毒素A重复单位(RARU)作为 一种载体分子。RARU的大尺寸(含有一个单一的多肽 MR of 104,000)、其免疫优势和佐剂性质及其作用 使其成为极具吸引力的携带者。 志贺氏菌荚膜多糖的研究。将与RARU结合。 将用结合物免疫多组小鼠，并进行抗体评估 对多糖和稀有物质的反应。这些结果将与 以前使用其他细菌毒素作为载体获得的结果。这个 RARU的使用可能在结合疫苗中有广泛的应用，并且可以 适用于多种来源的胶囊多糖的偶联 病原体的数量。 建议的商业应用： 重组艰难梭菌毒素结合疫苗的研制 作为囊膜载体分子的A重复单元(RARU) 多糖类可能是非常有效的，因为免疫优势和 ARU的佐剂特性。这个项目的结果可能会导致 开发对健康有重大价值的疫苗 世界各地的工业。

Even with the numerous advances made in vaccination programs, infectious diseases continue to pose serious problems to the health profession. In industrialized countries, opportunistic pathogens such as Clostridium difficile and Staphylococcus aereus continue to cause disease in hospitalized patients. Infections of infants and young children due to Hemophilus, Streptococcus, and Neisseria continue to be a serious health threat. In poorer countries, enteric infections are estimated to kill 10 to 12 million persons a year, most of these being under one year of age. Therefore, it is important to continue developing new approaches for vaccines. The results of studies by Drs. John Robbins and Rachel Schneerson at the National Institute of Child Health and Human Development show that vaccines comprised of capsular polysaccharides conjugated to carrier toxins such as tetanus, diphtheria toxin, and Pseudomonas exotoxin are highly effective. Based on these findings, we propose to evaluate the use of nontoxic recombinant C. difficile toxin A repeating units (rARU) as a carrier molecule. The large size of rARU (a single polypeptide with an Mr of 104,000), its immunodominant and adjuvant properties, and its role in human disease make it a highly attractive candidate as a carrier. Capsular polysaccharides from Shigella sp. will be conjugated to rARU. Groups of mice will be immunized with conjugate and evaluated for antibody response to polysaccharide and rARU. These results will be compared to previous results obtained using other bacterial toxins as carriers. The use of rARU may have widespread application in conjugate vaccines and may be suitable for conjugation with capsular polysaccharides from a variety of pathogens. Proposed commercial applications: Conjugate vaccines prepared using recombinant Clostridium difficile toxin A repeating units (rARU) as a carrier molecule for capsular polysaccharides may be highly effective, due to the immunodominant and adjuvant properties of ARU. The results of this project may lead to the development of vaccines that will be of significant value to the health industry around the world.