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 Voigt, Brian Granger, Robin G. Bombardi, Jennifer Govero, Qing Tan, Lorellin A. Durnell, Rhea N. Coler, Michael S. Diamond, James E. Crowe, Steven G. Reed, Larissa Thackray, Robert H. Carnahan, Neal Van Hoeven

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)402-414
Number of pages13
JournalMolecular Therapy - Methods and Clinical Development
Volume18
DOIs
StatePublished - Sep 11 2020

Keywords

  • antibody delivery
  • Gene-encoded antibody
  • monoclonal antibody
  • replicon
  • RNA delivery
  • RNA therapeutic
  • self-amplifying RNA

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    Erasmus, J. H., Archer, J., Fuerte-Stone, J., Khandhar, A. P., Voigt, E., Granger, B., Bombardi, R. G., Govero, J., Tan, Q., Durnell, L. A., Coler, R. N., Diamond, M. S., Crowe, J. E., Reed, S. G., Thackray, L., Carnahan, R. H., & Van Hoeven, N. (2020). Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection. Molecular Therapy - Methods and Clinical Development, 18, 402-414. https://doi.org/10.1016/j.omtm.2020.06.011