title: Ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent.
abstract: Current methods for inactivating filoviruses are limited to high doses of irradiation or formalin treatment, which may cause structural perturbations that are reflected by poor immunogenicity. In this report, we describe a novel inactivation technique for Zaire Ebola virus (ZEBOV) that uses the photoinduced alkylating probe 1,5-iodonaphthylazide (INA). INA is incorporated into lipid bilayers and, when activated by ultraviolet irradiation, alkylates the proteins therein. INA treatment of ZEBOV resulted in the complete loss of infectivity in cells. Results of electron microscopy and virus-capture assays suggested the preservation of conformational surface epitopes. Challenge with 50,000 pfu of INA-inactivated, mouse-adapted ZEBOV did not cause disease or death in mice. A single vaccination with INA-inactivated ZEBOV (equivalent to 5 x 10(4) pfu) protected mice against lethal challenge with 1000 pfu of ZEBOV. INA-inactivated virus induced a protective response in 100% of mice when administered 3 days before challenge. Thus, INA may have significant potential for the development of vaccines and immunotherapeutics for filoviruses and other enveloped viruses.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Warfield
authors.forename: Dana L
authors.initials: DL
authors.lastname: Swenson
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.forename: Warren V
authors.initials: WV
authors.lastname: Kalina
authors.forename: Mathias
authors.initials: M
authors.lastname: Viard
authors.forename: Mohamed
authors.initials: M
authors.lastname: Aitichou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chi
authors.forename: Sofi
authors.initials: S
authors.lastname: Ibrahim
authors.forename: Robert
authors.initials: R
authors.lastname: Blumenthal
authors.forename: Yossef
authors.initials: Y
authors.lastname: Raviv
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology* / Q000528:radiation effects; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis*; D000998:Antiviral Agents / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D015023:Democratic Republic of the Congo; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000187:drug effects* / Q000472:pathogenicity / Q000648:ultrastructure*; D005260:Female; D000882:Haplorhini; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010777:Photochemistry; D014709:Vero Cells; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D000477:Alkylating Agents; D000956:Antigens, Viral; D000998:Antiviral Agents; D001386:Azides; D014765:Viral Vaccines; C015298:iodonaphthylazide