以类风湿关节炎为代表的炎性关节炎，TNFα等促炎因子对病变起重要作用。生物制剂主要包括TNFα拮抗剂，改善难治性患者的疗效，但高昂的费用使其不能满足需求。国际上有针对TNFα疫苗的主动免疫研究，旨在让机体产生中和TNFα的抗体，以达注射剂量小，次数少，费用低，在所需要的时间内拮抗TNFα。我们在前一个国家自然基金《一种新型疫苗对小鼠胶原诱导关节炎的治疗效果及机制研究》中自行设计针对小鼠可溶性TNFα的多肽疫苗KLH-TNFα(4-23)。研究证实，疫苗克服小鼠的自身耐受，诱导了高滴度的TNFα抗体，用于CIA关节炎模型，减轻了小鼠四肢的炎症。为让疫苗构成及拮抗目标接近人体状况，本次申请将在前述研究基础上，设计并筛选人体TNFα多肽疫苗（我们已经筛选到符合要求的人TNFα抗原肽并且合成为疫苗），研究其在转人TNFα基因小鼠自发性关节炎中的疗效及作用机制，为将来可能进行的人体临床试验奠定基础。

Rheumatoid arthritis (RA) is one of the most common and representative disease with TNFα as the primary pro-inflammatory factor. Recently, the development of biological medications, especially TNFα antagonists, bring gospel to RA patients. However, TNFα cannot be popularized to the general public because of high cost. Active immunization against TNFα appeared internationally. Active immunization targeting TNFα aims at making body producing TNFα neutralizing antibody so that the excess TNFα could be neutralized through small doses administrations and less injection times. Our previous natural science foundation work has designed a new peptide vaccine KLH- TNFα(4-23) targeted murine soluble TNFα, which proved that the vaccine could elicit high titers of antibody by overcoming self-tolerance. Moreover, the peptide vaccine could ameliorate the symptom of collagen induced arthritis on mice and improve the general condition. In order to make the vaccine composition and use condition close to human body, our application which bases on the previous study aims at designing a peptide vaccine targeting soluble human TNFα, and exploring the effect and mechanism on idiopathic arthritis transgenic mice, laying the fundation for future clinical research.