Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity
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 engi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-09-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2020.1748979 |
| _version_ | 1797677307787214848 |
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| author | Katherine Schultheis Holly M Pugh Janet Oh Jacklyn Nguyen Bryan Yung Charles Reed Neil Cooch Jing Chen Jian Yan Kar Muthumani Laurent M. Humeau David B. Weiner Kate E. Broderick Trevor R. F. Smith |
| author_facet | Katherine Schultheis Holly M Pugh Janet Oh Jacklyn Nguyen Bryan Yung Charles Reed Neil Cooch Jing Chen Jian Yan Kar Muthumani Laurent M. Humeau David B. Weiner Kate E. Broderick Trevor R. F. Smith |
| author_sort | Katherine Schultheis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:42:48Z |
| format | Article |
| id | doaj.art-d9cb672e710345b8835668cbf603e147 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:42:48Z |
| publishDate | 2020-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-d9cb672e710345b8835668cbf603e1472023-09-22T08:51:48ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2020-09-011692165217510.1080/21645515.2020.17489791748979Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activityKatherine Schultheis0Holly M Pugh1Janet Oh2Jacklyn Nguyen3Bryan Yung4Charles Reed5Neil Cooch6Jing Chen7Jian Yan8Kar Muthumani9Laurent M. Humeau10David B. Weiner11Kate E. Broderick12Trevor R. F. Smith13Inovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsInovio PharmaceuticalsThe Wistar InstituteInovio PharmaceuticalsThe Wistar InstituteInovio PharmaceuticalsInovio PharmaceuticalsRespiratory 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.http://dx.doi.org/10.1080/21645515.2020.1748979respiratory syncytial virussingle-chain antibodyelectroporationactive immunophrophylaxisdna-encoded antibodycotton ratplasmid dna |
| spellingShingle | Katherine Schultheis Holly M Pugh Janet Oh Jacklyn Nguyen Bryan Yung Charles Reed Neil Cooch Jing Chen Jian Yan Kar Muthumani Laurent M. Humeau David B. Weiner Kate E. Broderick Trevor R. F. Smith Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity Human Vaccines & Immunotherapeutics respiratory syncytial virus single-chain antibody electroporation active immunophrophylaxis dna-encoded antibody cotton rat plasmid dna |
| title | Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity |
| title_full | Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity |
| title_fullStr | Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity |
| title_full_unstemmed | Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity |
| title_short | Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity |
| title_sort | active immunoprophylaxis with a synthetic dna encoded monoclonal anti respiratory syncytial virus scfv fc fusion protein confers protection against infection and durable activity |
| topic | respiratory syncytial virus single-chain antibody electroporation active immunophrophylaxis dna-encoded antibody cotton rat plasmid dna |
| url | http://dx.doi.org/10.1080/21645515.2020.1748979 |
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