Ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent

Kelly L. Warfield, Dana L. Swenson, Gene G. Olinger, Warren V. Kalina, Mathias Viard, Mohamed Aitichou, Xiaoli Chi, Sofi Ibrahim, Robert Blumenthal, Yossef Raviv, Sina Bavari, M. Javad Aman

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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 5104 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.

Original languageEnglish (US)
Pages (from-to)S276-S283
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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