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NEUTRALIZING HUMAN MONOCLONAL ANTIBODIES PREVENT ZIKA VIRUS INFECTION IN MACAQUES
Magnani, Diogo M. et al. | Date Issued: 2017
Author
Magnani, Diogo M.
Rogers, Thomas F.
Beutler, Nathan
Ricciardi, Michael J.
Bailey, Varian K.
Gonzalez Nieto, Lucas
Briney, Bryan
Sok, Devin
Le, Khoa
Strubel, Alexander
Gutman, Martin J.
Pedreño-Lopez, Núria
Grubaugh, Nathan D.
Silveira, Cassia G. T.
Maxwell, Helen S.
Domingues, Aline
Martins, Mauricio A.
Lee, David E.
Okwuazi, Erica E.
Jean, Sherrie
Strobert, Elizabeth A.
Chahroudi, Ann
Silvestri, Guido
Vanderford, Thomas H.
Kallas, Esper Georges
Desrosiers, Ronald C.
Bonaldo, Myrna C.
Whitehead, Stephen S.
Burton, Dennis R.
Watkins, David I.
Affilliation
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA;.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA;.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA;.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA;.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA;.
Universidade de São Paulo. Escola de Medicina. Divisão de Imunologia Clínica e Alergia. São Paulo, SP, Brasil.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA / Emory University. Department of Pediatrics. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Emory University. YerkesNational Primate Research Center. Atlanta, GA, USA.
Universidade de São Paulo. Escola de Medicina. Divisão de Imunologia Clínica e Alergia. São Paulo, SP, Brasil.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Infectious Diseases. Bethesda, MD, USA.
The Scripps Research Institute. International AIDS Vaccine Initiative Neutralizing Antibody Center. Department of Immunology and Microbiology. La Jolla, CA, USA / Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA.
University of Miami Leonard M. Miller School of Medicine. Department of Pathology. Miami, FL, USA.
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.
Keywords in Portuguese
Zika virus
Infecção
Prevenção
Anticorpos Monoclonais neutralizantes
 
Keywords
Zika virus
infection
prevention
neutralizing monoclonal antibodies
 
Publisher
American Association for the Advancement of Science
Citation
MAGNANI, Diogo M. et al. Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques. Science Translational Medicine, n.9, eaan8184, 8p, Oct. 2017.
DOI
10.1126/scitranslmed.aan8184
ISSN
1946-6234