Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity
| Autor: | David B. Weiner, Laurent Humeau, Jian Yan, Trevor R.F. Smith, Holly Pugh, Katherine Schultheis, Jing Chen, Janet Oh, Jacklyn Nguyen, Bryan S. Yung, Karuppiah Muthumani, Neil Cooch, Charles C. Reed, Kate E. Broderick |
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| Rok vydání: | 2020 |
| Předmět: |
electroporation
medicine.drug_class viruses 030231 tropical medicine Immunology Respiratory Syncytial Virus Infections Respiratory syncytial virus Antibodies Viral Monoclonal antibody Virus 03 medical and health sciences plasmid DNA 0302 clinical medicine Immunity In vivo Respiratory Syncytial Virus Vaccines medicine Animals Immunology and Allergy Tissue Distribution Sigmodontinae 030212 general & internal medicine Cotton rat Pharmacology DNA-encoded antibody biology Antibodies Monoclonal cotton rat virus diseases respiratory system active immunophrophylaxis biology.organism_classification Antibodies Neutralizing Virology Fusion protein single-chain antibody Monoclonal biology.protein Antibody Viral Fusion Proteins Research Article Research Paper |
| Zdroj: | Human Vaccines & Immunotherapeutics article-version (VoR) Version of Record |
| ISSN: | 2164-554X 2164-5515 |
| Popis: | Respiratory Syncytial virus (RSV) is a major threat to many vulnerable populations. There are currently no approved vaccines, and RSV remains a high unmet global medical need. Here we describe the employment of a novel synthetic DNA-encoded antibody technology platform to develop and deliver an engineered human DNA-encoded monoclonal antibody (dMAbTM) targeting the fusion protein (F) of RSV as a new approach to prevention or therapy of at risk populations. In in vivo models, a single administration of synthetic DNA-encoding the single-chain fragment variable-constant fragment (scFv-Fc) RSV-F dMAb resulted in robust and durable circulating levels of a functional antibody systemically and in mucosal tissue. In cotton rats, which are the gold-standard animals to model RSV infection, we observed sustained scFv-Fc RSV-F dMAb in the sera and lung-lavage samples, demonstrating the potential for both long-lasting immunity to RSV and effective biodistribution. The scFv-Fc RSV-F dMAb harbored in the sera exhibited RSV antigen-specific binding and potent viral neutralizing activity. Importantly, in vivo delivery of synthetic DNA-encoding, the scFv-Fc RSV-F dMAb protected animals against viral challenge. Our findings support the significance of dMAbs as a potential platform technology for durable protection against RSV disease. |
| Databáze: | OpenAIRE |
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