Safety and protective efficacy of INA-inactivated Venezuelan equine encephalitis virus: implication in vaccine development.
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.
Centre for Combat Casualty and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Anuj
A
Sharma
Paridhi
P
Gupta
Pamela J
PJ
Glass
Michael D
MD
Parker
Radha K
RK
Maheshwari
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D004202:Disinfectants / Q000494:pharmacology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity*; D004685:Encephalomyelitis, Venezuelan Equine / Q000517:prevention & control*; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology; D014774:Virulence; D038301:Virus Inactivation
D001386:Azides; D004202:Disinfectants; D012367:RNA, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; C015298:iodonaphthylazide