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Deinococcus Mn2+ -Peptide Complex: A Novel Approach to Alphavirus Vaccine Development

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Journal Article

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USAMRIID Frederick United States

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Chikungunya virus CHIKV, an Old World alphavirus and Venezuelan equine encephalitis virus VEEV, a New World alphavirus are the causative agents of debilitating diseases in humans. Over the past decade, CHIKV caused numerous outbreaks in the Asian and European countries and Americas making it an emerging pathogen bearing great global health importance. VEEV, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses. Live attenuated vaccines V3526 and CHIKV 18125 were developed against both VEEV and CHIKV but had to be retracted due to residual virulence in spite of being highly immunogenic during the clinical trials.Classical gamma irradiated virus vaccine development approach is limited by immunogenicity loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus inactivation. Thus, we have used an in vitro reconstituted radio protective antioxidant complex MDP, consisting of Mn2 , peptide and phosphate, derived from radio resistant bacteria Deinococcus radio durans in the present study which selectively protects proteins but not the nucleic acid from the radiation-induced oxidative damage as desired for safe and efficacious vaccine development. In this study, we demonstrate that V3526 and CHIKV 18125 irradiated in the presence of MDP have significant epitope preservation even at supra-lethal doses of radiation. Irradiated viruses were found to be completely inactivated via several in vitro and in vivo neonatal mice assays. V3526 inactivated in the presence of MDP elicited significantly higher antibody response upon immunization and also resulted in drastically improved protective efficacy in vivo.

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