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.
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。
