Active immunoprophylaxis with a synthetic DNA-encoded monoclonal anti-respiratory syncytial virus scFv-Fc fusion protein confers protection against infection and durable activity. Issue 9 (1st September 2020)

• Record Type: Journal Article
• Authors: Schultheis, Katherine; Pugh, Holly M; Oh, Janet; Nguyen, Jacklyn; Yung, Bryan; Reed, Charles; Cooch, Neil; Chen, Jing; Yan, Jian; Muthumani, Kar; Humeau, Laurent M.; Weiner, David B.; Broderick, Kate E.; Smith, Trevor R. F.
• Is Part Of: Human vaccines & immunotherapeutics. Volume 16:Issue 9(2020)
• Page Start: 2165
• Page End: 2175
• Publication Date: 2020-09-01
• Subjects: Respiratory syncytial virus -- single-chain antibody -- electroporation -- active immunophrophylaxis -- DNA-encoded antibody -- cotton rat -- plasmid DNA; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2020.1748979
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: 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 (dMAb TM ) 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.