Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection

Molecular Therapy: Methods & Clinical Development

Amit P. Khandhar¹  Robin G. Bombardi²  Jasmine Fuerte-Stone²  Jacob Archer³  Lorellin A. Durnell³  Brian Granger³  Robert H. Carnahan⁴  Larissa B. Thackray⁴  Steven G. Reed⁴  Rhea N. Coler⁵  Jesse H. Erasmus⁵  Jennifer Govero⁵  Qing Tan⁵  Neal Van Hoeven⁵  Michael S. Diamond⁵  Emily Voigt⁵  James E. Crowe, Jr.⁶ 

[1] Corresponding author: Jesse H. Erasmus, Pre-Clinical Vaccine Development, Infectious Disease Research Institute, Seattle, WA, USA.;Department of Microbiology, University of Washington, Seattle, WA, USA;HDT Biocorp, Seattle, WA, USA;Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA;Pre-Clinical Vaccine Development, Infectious Disease Research Institute, Seattle, WA, USA;The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 27232, USA;

关键词: Gene-encoded antibody;    monoclonal antibody;    RNA therapeutic;    RNA delivery;    antibody delivery;    replicon;   

DOI  :  

来源: DOAJ

【 摘 要 】

Monoclonal antibody (mAb) therapeutics are an effective modality for the treatment of infectious, autoimmune, and cancer-related diseases. However, the discovery, development, and manufacturing processes are complex, resource-consuming activities that preclude the rapid deployment of mAbs in outbreaks of emerging infectious diseases. Given recent advances in nucleic acid delivery technology, it is now possible to deliver exogenous mRNA encoding mAbs for in situ 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.

【 授权许可】

Unknown