Deinococcus Mn 2+ -peptide complex: A novel approach to alphavirus vaccine development

Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the ot...

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Veröffentlicht in:Vaccine 2017-06, Vol.35 (29), p.3672
Hauptverfasser: Gayen, Manoshi, Gupta, Paridhi, Morazzani, Elaine M, Gaidamakova, Elena K, Knollmann-Ritschel, Barbara, Daly, Michael J, Glass, Pamela J, Maheshwari, Radha K
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container_end_page
container_issue 29
container_start_page 3672
container_title Vaccine
container_volume 35
creator Gayen, Manoshi
Gupta, Paridhi
Morazzani, Elaine M
Gaidamakova, Elena K
Knollmann-Ritschel, Barbara
Daly, Michael J
Glass, Pamela J
Maheshwari, Radha K
description Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, 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. In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma-inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost-effective manner.
doi_str_mv 10.1016/j.vaccine.2017.05.016
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However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. 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subjects Alphavirus Infections - prevention & control
Animals
Bacterial Proteins - isolation & purification
Bacterial Proteins - metabolism
Chikungunya virus - immunology
Chikungunya virus - radiation effects
Deinococcus - chemistry
Disease Models, Animal
Encephalitis Virus, Venezuelan Equine - immunology
Encephalitis Virus, Venezuelan Equine - radiation effects
Female
Gamma Rays
Manganese - metabolism
Mice, Inbred BALB C
Radiation-Protective Agents - metabolism
Vaccines, Inactivated - administration & dosage
Vaccines, Inactivated - immunology
Vaccines, Inactivated - isolation & purification
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
Viral Vaccines - isolation & purification
Virus Inactivation
title Deinococcus Mn 2+ -peptide complex: A novel approach to alphavirus vaccine development
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