Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques
| Autor: | Michael J. Ricciardi, Diogo M. Magnani, Cassia G. T. Silveira, Sherrie Jean, David E. Lee, Dennis R. Burton, Elizabeth Strobert, Lucas Gonzalez-Nieto, Nathan D. Grubaugh, Aline Domingues, Myrna C. Bonaldo, Guido Silvestri, Varian K. Bailey, Devin Sok, Khoa Le, Esper G. Kallas, Bryan Briney, Ann Chahroudi, Thomas H. Vanderford, Nathan Beutler, David I. Watkins, Thomas F. Rogers, Nuria Pedreño-Lopez, Erica E. Okwuazi, Stephen S. Whitehead, Mauricio A. Martins, Martin J. Gutman, Alexander Strubel, Helen S. Maxwell, Ronald C. Desrosiers |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class 030106 microbiology Viremia Monoclonal antibody Article Virus Zika virus 03 medical and health sciences Immunity medicine Animals Humans Fetus biology Zika Virus Infection Antibodies Monoclonal General Medicine Viral Load biology.organism_classification medicine.disease Antibodies Neutralizing Virology Immunity Humoral 030104 developmental biology Immunology biology.protein Macaca Antibody Viral load |
| Zdroj: | Science Translational Medicine. 9 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | 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 Fc-gamma receptor (FcγR) binding, thus eliminating potential therapy-mediated antibody-dependent enhancement (ADE). We administered a cocktail of these three nmAbs to nonhuman primates (NHP) one day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum following challenge. Given that numerous Abs have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses. |
| Databáze: | OpenAIRE |
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