Intramuscular Adeno-Associated Virus-Mediated Expression of Monoclonal Antibodies Provides 100% Protection Against Ebola Virus Infection in Mice

Laura P. Van Lieshout, Geoff Soule, Debra Sorensen, Kathy L. Frost, Shihua He, Kevin Tierney, David Safronetz, Stephanie A. Booth, Gary P. Kobinger, Xiangguo Qiu, Sarah K. Wootton

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The 2013-2016 West Africa outbreak demonstrated the epidemic potential of Ebola virus and highlighted the need for counter strategies. Monoclonal antibody (mAb)-based therapies hold promise as treatment options for Ebola virus infections. However, production of clinical-grade mAbs is labor intensive, and immunity is short lived. Conversely, adeno-associated virus (AAV)-mediated mAb gene transfer provides the host with a genetic blueprint to manufacture mAbs in vivo, leading to steady release of antibody over many months. Here we demonstrate that AAV-mediated expression of nonneutralizing mAb 5D2 or 7C9 confers 100% protection against mouse-adapted Ebola virus infection, while neutralizing mAb 2G4 was 83% protective. A 2-component cocktail, AAV-2G4/ AAV-5D2, provided complete protection when administered 7 days prior to challenge and was partially protective with a 3-day lead time. Finally, AAV-mAb therapies provided sustained protection from challenge 5 months following AAV administration. AAVmAb may be a viable alternative strategy for vaccination against emerging infectious diseases.

Original languageEnglish (US)
Pages (from-to)916-925
Number of pages10
JournalJournal of Infectious Diseases
Volume217
Issue number6
DOIs
StatePublished - Mar 5 2018
Externally publishedYes

Keywords

  • Adeno-associated virus
  • Ebola virus
  • Hemorrhagic fever
  • Neutralizing antibody
  • Vaccine
  • Vectored immunoprophylaxis
  • ZMapp

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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