乙型脑炎病毒所诱导人源抗体中对寨卡病毒具交叉保护作用抗体鉴定及其保护机制研究

黄病毒属病毒【如乙型脑炎病毒（JEV）和寨卡病毒（ZIKV）】间交叉反应性抗体对异型病毒的感染具有双重作用（交叉保护抗体和交叉致病性抗体分别介导保护和致病作用）。但JEV和ZIKV间交叉保护性抗体和交叉致病性抗体识别的关键序列尚未阐明。本项目首先探讨JEV免疫人诱导的可交叉识别ZIKV免疫原M、E和NS1的人源抗体IgG体内外对ZIKV感染的作用；基于覆盖ZIKV-M、E和NS1的重叠肽库，采用负载多肽的微珠鉴定JEV/ZIKV交叉保护性或交叉致病性抗体IgG识别的关键肽序列；利用负载混合肽的微珠采用正向和反向两种策略从JEV免疫诱导的人源抗体IgG中分离JEV/ZIKV交叉保护性IgG；最后系统研究所纯化JEV/ZIKV交叉保护性IgG对ZIKV感染的乳鼠和孕鼠的防治作用。本项目有望为研发可用于紧急防治重症寨卡疾病的人源抗体药物奠定基础，也将为安全有效的JEV和ZIKV疫苗研制提供线索。

Flaviviruses【like Japanese encephalitis virus (JEV) and Zika virus (ZIKV)】-cross-reactive antibodies have dual roles in heterologous flavivirus infection (cross-protective and cross-pathogenic antibodies mediate cross-protection and pathogenesis, respectively). But, the key amino acid sequences recognized by JEV/ZIKV-cross-protective and cross-pathogenic antibodies are uncertain. The present subject is designed to firstly explore the roles of ZIKV-M-, E-, NS1-targeting human antibodies IgG induced by JEV vaccination in ZIKV infection in vitro and in vivo; Secondly, based on the overlapping peptides pool covering ZIKV individual proteins (M, E and NS1)，microbeads coated with individual peptide are used to identity the key peptide sequence recognized by JEV/ZIKV-cross-protective or cross-pathogenic antibodies IgG; Subsequently, microbeads coated with peptide pool are used to purify (positive-selection or negative-selection) JEV/ZIKV-cross-protective IgG from JEV vaccination-induced human antibodies; Finally, to systematically clarify the preventive and therapeutic effects of purified JEV/ZIKV-cross-protective IgG on ZIKV infection using mouse neonate and pregnant mouse models. This study is expected to lay the foundation for the development of human antibody drugs for emergent prevention and therapy of severe Zika diseases, and will also provide clues for the development of safe and effective JEV/ZIKV vaccines.