In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus
| Autor: | Ghiabe Guibinga, Janess M. Mendoza, David B. Weiner, Laurent Humeau, Stephanie Ramos, Jian Yan, Sagar B. Kudchodkar, Trevor R.F. Smith, Kanika Asija, Jeffrey W. Allen, Piyush Borole, Jing Chen, Martina Beltramello, Ami Patel, Mamadou A. Bah, Karin Stettler, Davide Corti, Rianne Esquivel, Amy C. Durham, Hyeree Choi, Daniel H. Park, Shareef Shaheen, Kate E. Broderick, Karuppiah Muthumani |
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| Rok vydání: | 2019 |
| Předmět: |
Primates
medicine.drug_class Antibodies Viral DNA-encoded monoclonal antibody infectious diseases Monoclonal antibody Zika virus Mice 03 medical and health sciences 0302 clinical medicine Viral Envelope Proteins In vivo antibody Drug Discovery Genetics medicine Animals Humans Neutralizing antibody Molecular Biology 030304 developmental biology Pharmacology DMAb 0303 health sciences biology Zika Virus Infection Antibodies Monoclonal Outbreak DNA Zika Virus immunoprophylaxis protection biology.organism_classification Antibodies Neutralizing Virology Rhesus macaque Infectious disease (medical specialty) 030220 oncology & carcinogenesis biology.protein Molecular Medicine Original Article Antibody rhesus macaque |
| Zdroj: | Molecular Therapy |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2019.03.005 |
| Popis: | Zika virus (ZIKV) infection is endemic to several world regions, and many others are at high risk for seasonal outbreaks. Synthetic DNA-encoded monoclonal antibody (DMAb) is an approach that enables in vivo delivery of highly potent mAbs to control infections. We engineered DMAb-ZK190, encoding the mAb ZK190 neutralizing antibody, which targets the ZIKV E protein DIII domain. In vivo-delivered DMAb-ZK190 achieved expression levels persisting >10 weeks in mice and >3 weeks in non-human primate (NHPs), which is protective against ZIKV infectious challenge. This study is the first demonstration of infectious disease control in NHPs following in vivo delivery of a nucleic acid-encoded antibody, supporting the importance of this new platform. Esquivel et al. deliver DNA-encoded ZK190 antibody (DMAb-ZK190) by intramuscular administration. DMAb-ZK190 targets the E protein of Zika virus, and it controls Zika virus infection in mice and non-human primates when delivered prior to infection, offering an alternative strategy for rapid protection. |
| Databáze: | OpenAIRE |
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