2019
DOI: 10.1016/j.ymthe.2019.03.005
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In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus

Abstract: 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 … Show more

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Cited by 45 publications
(54 citation statements)
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“…Conventional mAbs remain an expensive approach from a manufacturing perspective so that a simple, cost-effective passive immunization strategy inducing sustained in vivo production would be extremely valuable. dMAbs, a DNA plasmid encoding mAbs have the potential to circumvent cost constraints and provide durable immunity, perhaps for the duration of an influenza pandemic or season 2427 . Here we tested 2-12C dMAb in the pig influenza model and although the serum concentration of in vivo expressed dMAb was 100 times lower (∼1 μg/ml) than in pigs given the recombinant protein at 15 mg/kg (∼100 μg/ml) we observed significant protection against disease pathology in the lungs.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Conventional mAbs remain an expensive approach from a manufacturing perspective so that a simple, cost-effective passive immunization strategy inducing sustained in vivo production would be extremely valuable. dMAbs, a DNA plasmid encoding mAbs have the potential to circumvent cost constraints and provide durable immunity, perhaps for the duration of an influenza pandemic or season 2427 . Here we tested 2-12C dMAb in the pig influenza model and although the serum concentration of in vivo expressed dMAb was 100 times lower (∼1 μg/ml) than in pigs given the recombinant protein at 15 mg/kg (∼100 μg/ml) we observed significant protection against disease pathology in the lungs.…”
Section: Discussionmentioning
confidence: 99%
“…Alternative in vivo antibody gene transfer strategies using DNA, RNA or viral vectors have shown that antibody genes can be stably maintained in the host tissue, resulting in potent and long-term expression of mAbs in the body following a single administration 1723 . DNA plasmid encoded mAbs (dMAbs), which are delivered to muscle tissue, are a novel approach with the potential to provide durable immunity 2426 . The plasmid DNA is well-tolerated and nonintegrating, does not require cold-chain distribution, can be delivered repeatedly and is relatively inexpensive to produce.…”
mentioning
confidence: 99%
“…Plasmid DNA-encoded mAbs (pDNA-mAbs) are engineered to carry synthetic antibody genes, similar to AAV-mAb platforms. The literature describes that pDNA-mAbs can exhibit peak serum concentrations after just 2 weeks and then can express at consistent levels for 2-3 months and decline thereafter as the plasmid is lost from cells and then cleared from the serum due to the natural half-life of immunoglobulin G (IgG) [36][37][38][39][40][41]. Long-term small animal studies show the total duration of pDNA-mAb expression to be at least 1 year [42,43].…”
Section: Synthetic Dnamentioning
confidence: 99%
“…Xu et al reported Synthetic DNA vaccines: prime time is approaching Gary and Weiner 25 [33 ]. This platform continues to advance and DMAbs targeting influenza A and B [34,35], dengue [36], Chikungunya [37 ], Zika [38 ], and Ebola [35,39] with of protection in animal models.…”
Section: Syndna Biologics In the Preclinical Settingmentioning
confidence: 99%