寨卡病毒感染后人类抗体库的差异及其对血清学诊断和疾病结局的影响。
Differential human antibody repertoires following Zika infection and the implications for serodiagnostics and disease outcome.
机构信息
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA.
Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.
出版信息
Nat Commun. 2019 Apr 26;10(1):1943. doi: 10.1038/s41467-019-09914-3.
Zika virus (ZIKV) outbreak in Americas led to extensive efforts to develop vaccines and ZIKV-specific diagnostics. In the current study, we use whole genome phage display library spanning the entire ZIKV genome (ZIKV-GFPDL) for in-depth immune profiling of IgG and IgM antibody repertoires in serum and urine longitudinal samples from individuals acutely infected with ZIKV. We observe a very diverse IgM immune repertoire encompassing the entire ZIKV polyprotein on day 0 in both serum and urine. ZIKV-specific IgG antibodies increase 10-fold between day 0 and day 7 in serum, but not in urine; these are highly focused on prM/E, NS1 and NS2B. Differential antibody affinity maturation is observed against ZIKV structural E protein compared with nonstructural protein NS1. Serum antibody affinity to ZIKV-E protein inversely correlates with ZIKV disease symptoms. Our study provides insight into unlinked evolution of immune response to ZIKV infection and identified unique targets for ZIKV serodiagnostics.
寨卡病毒（ZIKV）在美洲的爆发促使人们大力研发疫苗和寨卡病毒特异性诊断方法。在本研究中，我们使用了覆盖整个寨卡病毒基因组的全基因组噬菌体展示文库（ZIKV-GFPDL），对急性感染寨卡病毒的个体的血清和尿液纵向样本中的 IgG 和 IgM 抗体库进行深入的免疫分析。我们观察到，在血清和尿液中，在第 0 天就存在着涵盖整个寨卡病毒多蛋白的非常多样化的 IgM 免疫库。在血清中，寨卡病毒特异性 IgG 抗体在第 0 天到第 7 天之间增加了 10 倍，但在尿液中没有增加；这些抗体高度集中在 prM/E、NS1 和 NS2B 上。与非结构蛋白 NS1 相比，针对寨卡病毒结构 E 蛋白的抗体亲和力呈现出不同的成熟。血清抗体对寨卡病毒-E 蛋白的亲和力与寨卡病毒病的症状呈负相关。我们的研究深入了解了针对寨卡病毒感染的免疫反应的非连锁进化，并确定了寨卡病毒血清学诊断的独特靶标。
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