Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus

开发皮内 DNA 疫苗输送策略以实现针对呼吸道合胞病毒的单剂量免疫

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作者:Trevor R F Smith, Katherine Schultheis, Matthew P Morrow, Kimberly A Kraynyak, Jay R McCoy, Kevin C Yim, Karuppiah Muthumani, Laurent Humeau, David B Weiner, Niranjan Y Sardesai, Kate E Broderick

Abstract

Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy.

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