iodonaphthylazide and Disease-Models--Animal

We have previously shown that a hydrophobic alkylating compound, 1,5-iodonaphthyl-azide (INA) can efficiently inactivate the virulent strain of Venezuelan equine encephalitis virus (VEEV), V3000 in vitro. In this study, we have evaluated the safety of INA-inactivated V3000 and V3526 and the protective efficacy of INA-inactivated V3000. INA-inactivated V3000 and V3526 did not cause disease in suckling mice. RNA isolated from the INA-inactivated V3000 and V3526 was also not infectious. Immunization of adult mice with INA-inactivated V3000 induced an anti-VEEV antibody response and protected mice from virulent VEEV challenge. The protective efficacy of INA-inactivated V3000 increased with the use of adjuvants. Results suggest that inactivation of enveloped viruses by INA may occur by two independent mechanisms and the INA-inactivated VEEV elicit a protective antibody response in mice.

Topics: Animals; Azides; Cytopathogenic Effect, Viral; Disease Models, Animal; Disinfectants; Encephalitis Virus, Venezuelan Equine; Encephalomyelitis, Venezuelan Equine; Mice; Microbial Viability; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Survival Analysis; Vaccines, Inactivated; Viral Plaque Assay; Viral Vaccines; Virulence; Virus Inactivation

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.

Topics: Alkylating Agents; Animals; Antigens, Viral; Antiviral Agents; Azides; Chlorocebus aethiops; Democratic Republic of the Congo; Disease Models, Animal; Ebolavirus; Female; Haplorhini; Hemorrhagic Fever, Ebola; Mice; Mice, Inbred C57BL; Photochemistry; Vero Cells; Viral Vaccines