塞内卡谷病毒（SVV）中和抗体筛选及其中和机制研究

塞内卡谷病毒(Seneca Valley Virus，SVV)是近年来从猪体上新发现的一个传染病病原，其感染与猪的特发性水泡疾病相关。目前人们对致病机制知之甚少，从而限制了该病防控性产品的研发和疾病的控制。以中和抗体介导的体液免疫在病毒感染控制中起着重要的作用。我们前期研究筛选获得多株SVV单克隆中和抗体(如2G6和5A1)，对SVV不同毒株的中和效果存在差异。鉴于此，本研究拟利用病毒学、免疫学和结构生物学技术开展以下研究：(1)筛选SVV优势中和抗体并确定2G6和5A1在SVV复制周期中发挥中和作用的关键阶段；(2)解析SVV-2G6/5A1-Fab复合物的晶体结构、揭示中和表位并阐明其中和机制；(3)基于结构生物学改造SVV并探究其免疫原性和致病性。该研究为从结构生物学角度剖析中和抗体作用机制，为进一步阐明SVV致病机理和改造提升病毒的免疫效果等奠定基础，具有重要的理论意义和应用潜力。

Seneca Valley Virus (SVV) is the etiological agent of porcine idiopathic vesicular disease(PIVD) and epidemic transient neonatal losses(ETNL) in pigs in several Americas and Asia countries. SVV has recently expanded in major swine-producing countries around the world, including the United States, Brazil, Canada, Thailand, China and Vietnam. As an emerging picornavirus of swine, many aspects of SVV interaction with the host and the pathogenic mechanism remain unknown, which limits the development of preventive vaccines and the control of this disease. Humoral responses mediated by neutralizing antibodies（NAbs）play an important role in viral infection and pathogenesis by preventing different steps of life cycle such as virion entry into target cells and virus budding from infected cells, as well as engaging Fc receptors on immune cells to activate antiviral responses. Our previous studies we have identified several neutralizing antibodies (such as 2G6 and 5A1) to SVV with different neutralizing character against SVV strains HB-CH-2016 and LNSY-01, while the mechanisms of neutralization of SVV by 2G6 and 5A1 were unclear. Based on the above findings, further studies will conducted to the following questions through the virological, immunological and structural biology techniques. (1). Furtherly screen monoclonal antibodies with SVV-neutralizing activity, and determine the key steps of SVV replication cycle by neutralization antibodies to inhibit virus infection. (2). Illuminate the molecular details of neutralizing epitopes and unveil the mechanisms among the interplays of virus-receptor-Nabs based on the analyzing the crystal structures of SVV-2G6/5A1-Fab complex. (3). Study the stability, immunogenicity and pathogenicity of recombinant SVV mutants by mutating the critical amino acids of antibody variable region. Completion of this project will be useful to provide new insights into the neutralizing mechanism and pathogenesis of SVV, which helping to provide a theoretical basis for the research and development of biological agents such as novel vaccine and antiviral agents against SVV.