PDF(Pubmed)
Abstract：
Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy.
摘要：
先天性寨卡病毒（ZIKV）感染导致多达14％的ZIKV感染母亲所生的婴儿出现神经发育缺陷。中和抗体是保护性免疫的关键组成部分。这里,我们证明血浆IgM有助于妊娠期的ZIKV免疫，调解中和长达3个月的症状后。从一名感染ZIKV的孕妇身上，我们分离了一种五聚体ZIKV特异性IgM(DH1017。IgM）表现出依赖于IgM同种型的超效ZIKV中和。DH1017.IgM靶向结构域II内的包膜二聚体表位。病毒体上的表位排列与DH1017的所有十个抗原结合位点的同时接合相容。IgM,IgG不可用的溶液。DH1017.IgM在致命性ZIKV攻击后比表达为IgG时更有效地保护小鼠免受病毒血症。我们的发现确定了IgM同种型抗体在保护ZIKV和DH1017中的作用。IgM作为一种安全有效的候选免疫治疗剂,特别是在怀孕期间。
