Rogers Thomas F, Goodwin Eileen C, Briney Bryan, Sok Devin, Beutler Nathan, Strubel Alexander, Nedellec Rebecca, Le Khoa, Brown Michael E, Burton Dennis R, Walker Laura M
Department of Immunology and Microbiology, the Scripps Research Institute, La Jolla, CA 92037, USA.
Adimab LLC, Lebanon, NH 03766, USA.
Sci Immunol. 2017 Aug 18;2(14). doi: 10.1126/sciimmunol.aan6809.
Zika virus (ZIKV) shares a high degree of homology with dengue virus (DENV), suggesting that preexisting immunity to DENV could affect immune responses to ZIKV. We have tracked the evolution of ZIKV-induced B cell responses in three DENV-experienced donors. The acute antibody (plasmablast) responses were characterized by relatively high somatic hypermutation and a bias toward DENV binding and neutralization, implying the early activation of DENV clones. A DENV-naïve donor in contrast showed a classical primary plasmablast response. Five months after infection, the DENV-experienced donors developed potent type-specific ZIKV neutralizing antibody responses in addition to DENV cross-reactive responses. Because cross-reactive responses were poorly neutralizing and associated with enhanced ZIKV infection in vitro, preexisting DENV immunity could negatively affect protective antibody responses to ZIKV. The observed effects are epitope-dependent, suggesting that a ZIKV vaccine should be carefully designed for DENV-seropositive populations.
寨卡病毒（ZIKV）与登革病毒（DENV）具有高度同源性，这表明对DENV的既往免疫可能会影响对ZIKV的免疫反应。我们追踪了三名有DENV感染经历的供体中ZIKV诱导的B细胞反应的演变。急性抗体（浆母细胞）反应的特征是体细胞超突变相对较高，且偏向于DENV结合和中和，这意味着DENV克隆的早期激活。相比之下，一名未接触过DENV的供体表现出典型的原发性浆母细胞反应。感染五个月后，有DENV感染经历的供体除了产生DENV交叉反应性反应外，还产生了有效的型特异性ZIKV中和抗体反应。由于交叉反应性反应的中和能力较差，且在体外与ZIKV感染增强有关，因此既往的DENV免疫可能会对ZIKV的保护性抗体反应产生负面影响。观察到的效应是表位依赖性的，这表明应为DENV血清阳性人群精心设计ZIKV疫苗。
