Intramuscular Adeno-Associated Virus–Mediated Expression of Monoclonal Antibodies Provides 100% Protection Against Ebola Virus Infection in Mice. (20th January 2018)

• Record Type: Journal Article
• Authors: van Lieshout, Laura P; Soule, Geoff; Sorensen, Debra; Frost, Kathy L; He, Shihua; Tierney, Kevin; Safronetz, David; Booth, Stephanie A; Kobinger, Gary P; Qiu, Xiangguo; Wootton, Sarah K
• Is Part Of: Journal of infectious diseases. Volume 217:Number 6(2018)
• Page Start: 916
• Page End: 925
• Publication Date: 2018-01-20
• Subjects: Ebola virus -- hemorrhagic fever -- vaccine -- neutralizing antibody -- ZMapp -- adeno-associated virus -- vectored immunoprophylaxis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix644
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Adeno-associated virus–mediated expression of monoclonal antibodies confers 100% protection in mice when administered intramuscularly as early as 7 days prior to lethal mouse adapted Ebola virus challenge, offering an alternative strategy to traditional vaccination. 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. AAV-mAb may be a viable alternative strategy for vaccination against emerging infectious diseases.