| Literature DB >> 28978754 |
Diogo M Magnani1, Thomas F Rogers2, Nathan Beutler2, Michael J Ricciardi1, Varian K Bailey1, Lucas Gonzalez-Nieto1, Bryan Briney2, Devin Sok2, Khoa Le2, Alexander Strubel2, Martin J Gutman1, Núria Pedreño-Lopez1, Nathan D Grubaugh2, Cassia G T Silveira3, Helen S Maxwell1, Aline Domingues1, Mauricio A Martins1, David E Lee4, Erica E Okwuazi4, Sherrie Jean4, Elizabeth A Strobert4, Ann Chahroudi4,5, Guido Silvestri4, Thomas H Vanderford4, Esper G Kallas3, Ronald C Desrosiers1, Myrna C Bonaldo6, Stephen S Whitehead7, Dennis R Burton8,9, David I Watkins10.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28978754 PMCID： PMC6155977 DOI： 10.1126/scitranslmed.aan8184
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956