探讨原始抗原效应对禽类流感病毒感染及免疫应答的影响

项目名称： 探讨原始抗原效应对禽类流感病毒感染及免疫应答的影响

项目编号： No.31502048

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 水产学、兽医学

项目作者： 李桂梅

作者单位： 青岛农业大学

项目金额： 21万元

中文摘要： 可刺激机体产生针对不同亚型流感病毒保护性免疫的通用型流感疫苗是近期研究热点。过往研究发现2009甲型流感病毒H1N1感染或免疫后，机体产生体液免疫应答具有广泛交叉反应性。推测与机体已有的少数具有交叉反应性的记忆B细胞被激活并迅速增殖分化有关。然而，既往感染或疫苗接种史可能会削弱后续的免疫应答，即出现原始抗原效应（original antigenic sin，OAS)，影响免疫效果。本课题将（1）探讨禽类是否存在OAS效应及在禽类中记忆性免疫对异源病毒免疫应答的影响。（2）探索可能削弱OAS效应、促进机体对异源病毒产生保护性免疫应答的途径。（3）从感染了与免疫原同源或异源的流感病毒小鼠中制备单克隆抗体，对单克隆抗体进行解析，比较同源与异源流感病毒感染后抗体的交叉保护作用，推测具有广泛交叉保护作用的抗原表位。本研究将为开发通用型流感疫苗以及合理设计疫苗接种程序提供一定实验依据。

中文关键词： 家禽；体液免疫应答；疫苗；抗体；免疫记忆

英文摘要： In the past a few years, great efforts have been made to develop universal influenza vaccines targeting both homologous and heterologous influenza virus infections. However, rational design of universal vaccine relies on thorough understanding of the host immune response following infection or immunization. Previously, we found that following 2009 novel influenza H1N1 infection or vaccination, human developed broadly cross-reactive humoral immune responses. We hypothesize that this is due to the activation of rare cross-reactive memory B cells derived from previous exposure. On the other hand, the immune history, including infection and immunization, may impair the secondary immune response, this effect is named as “original antigenic sin” (OAS). In this study, we will focus on the following scientific questions: (1) Does the OAS response to influenza infection exist in poultry? (2) How to alleviate the OAS effect and improve the immune response to heterologous virus infection? (3) Could heterologous influenza vaccination/infection induce more broadly cross-reactive monoclonal antibodies than homologous influenza vaccination/infection? This study will provide experimental basis for the development of universal vaccine and rational design of immunization strategies.

英文关键词： poultry;humoral immune response;vaccine;antibody;immune memory