当前位置: X-MOL 学术Sci. Transl. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques.
Science Translational Medicine ( IF 17.1 ) Pub Date : 2017-10-04 , DOI: 10.1126/scitranslmed.aan8184
Diogo M Magnani 1 , Thomas F Rogers 2 , Nathan Beutler 2 , Michael J Ricciardi 1 , Varian K Bailey 1 , Lucas Gonzalez-Nieto 1 , Bryan Briney 2 , Devin Sok 2 , Khoa Le 2 , Alexander Strubel 2 , Martin J Gutman 1 , Núria Pedreño-Lopez 1 , Nathan D Grubaugh 2 , Cassia G T Silveira 3 , Helen S Maxwell 1 , Aline Domingues 1 , Mauricio A Martins 1 , David E Lee 4 , Erica E Okwuazi 4 , Sherrie Jean 4 , Elizabeth A Strobert 4 , Ann Chahroudi 4, 5 , Guido Silvestri 4 , Thomas H Vanderford 4 , Esper G Kallas 3 , Ronald C Desrosiers 1 , Myrna C Bonaldo 6 , Stephen S Whitehead 7 , Dennis R Burton 2, 8 , David I Watkins 1
Affiliation  

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient—SMZAb1, SMZAb2, and SMZAb5—directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.



中文翻译:

中和性人类单克隆抗体可防止猕猴感染寨卡病毒。

迫切需要预防母体寨卡病毒(ZIKV)感染及其随后的胎儿发育并发症的疗法。我们从感染ZIKV的患者的成浆细胞中分离了三种针对ZIKV的有效单克隆抗体(nmAbs),分别针对该病毒的两个不同域,分别为SMZAb1,SMZAb2和SMZAb5。我们用Fc LALA突变工程化了这些nmAb,这些突变消除了Fcγ受体的结合,从而消除了潜在的治疗介导的抗体依赖性增强作用。我们在用ZIKV攻击前1天将这三种nmAb的混合物施用于非人类灵长类动物,并证明了nmAb完全阻止了攻击后血清中的病毒血症。鉴于众多抗体在人体中具有非凡的安全性,

更新日期:2017-10-04
down
wechat
bug