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Updated: Feb 21, 2026
Quantification of Antibody-dependent Enhancement of the Zika Virus in Primary Human Cells
Published on: January 18, 2019
Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques
Diogo M Magnani1, Thomas F Rogers2, Nathan Beutler2
1Department of Pathology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, 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.
Insights
Monoclonal antibodies (nmAbs) targeting Zika virus (ZIKV) were developed to prevent fetal complications. A novel nmAb cocktail completely prevented ZIKV viremia in nonhuman primates, offering potential protection for pregnant women.
Area of Science:
- Virology
- Immunology
- Maternal-Fetal Medicine
Background:
- Maternal Zika virus (ZIKV) infection poses severe risks to fetal development, necessitating urgent preventive therapies.
- Existing ZIKV therapies lack sufficient efficacy or carry potential risks like antibody-dependent enhancement.
Purpose of the Study:
- To develop and evaluate a novel monoclonal antibody (nmAb) cocktail for preventing ZIKV infection and associated fetal complications.
- To engineer ZIKV-neutralizing nmAbs to eliminate Fcγ receptor binding and prevent antibody-dependent enhancement.
Main Methods:
- Isolation of three potent ZIKV-neutralizing nmAbs (SMZAb1, SMZAb2, SMZAb5) from a ZIKV-infected patient.
- Engineering of nmAbs with Fc LALA mutations to abrogate Fcγ receptor binding.
- Administration of an nmAb cocktail to nonhuman primates one day prior to ZIKV challenge.
Main Results:
- The engineered nmAb cocktail completely prevented viremia in serum following ZIKV challenge in nonhuman primates.
- The Fc LALA mutations successfully eliminated potential therapy-mediated antibody-dependent enhancement.
Conclusions:
- A cocktail of engineered monoclonal antibodies effectively neutralizes Zika virus and prevents viremia.
- This nmAb cocktail demonstrates significant potential for rapid development as a protective therapy for pregnant women and their fetuses against ZIKV infection.
