Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection
Jesse H. Erasmus, Jacob Archer, Jasmine Fuerte-Stone, Amit P. Khandhar, Emily A. Voigt, Brian Granger, Robin Bombardi, Jennifer Govero, Qing Tan, Lorellin A. Durnell, Rhea N. Coler, Michael Diamond, James E. Crowe, Steven G. Reed, Larissa B. Thackray, Robert H. Carnahan, Neal Van Hoeven
Abstract
expression following intravenous (i.v.) infusion of lipid nanoparticle-encapsulated mRNA. However, the requirement for i.v. administration limits the application to settings where infusion is an option, increasing the cost of treatment. As an alternative strategy, and to enable intramuscular (IM) administration of mRNA-encoded mAbs, we describe a nanostructured lipid carrier for delivery of an alphavirus replicon encoding a previously described highly neutralizing human mAb, ZIKV-117. Using a lethal Zika virus challenge model in mice, our studies show robust protection following alphavirus-driven expression of ZIKV-117 mRNA when given by IM administration as pre-exposure prophylaxis or post-exposure therapy.