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 |
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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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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.</description><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2017.05.016</identifier><identifier>PMID: 28576570</identifier><language>eng</language><publisher>Netherlands</publisher><subject><![CDATA[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]]></subject><ispartof>Vaccine, 2017-06, Vol.35 (29), p.3672</ispartof><rights>Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28576570$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gayen, Manoshi</creatorcontrib><creatorcontrib>Gupta, Paridhi</creatorcontrib><creatorcontrib>Morazzani, Elaine M</creatorcontrib><creatorcontrib>Gaidamakova, Elena K</creatorcontrib><creatorcontrib>Knollmann-Ritschel, Barbara</creatorcontrib><creatorcontrib>Daly, Michael J</creatorcontrib><creatorcontrib>Glass, Pamela J</creatorcontrib><creatorcontrib>Maheshwari, Radha K</creatorcontrib><title>Deinococcus Mn 2+ -peptide complex: A novel approach to alphavirus vaccine development</title><title>Vaccine</title><addtitle>Vaccine</addtitle><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.</description><subject>Alphavirus Infections - prevention & control</subject><subject>Animals</subject><subject>Bacterial Proteins - isolation & purification</subject><subject>Bacterial Proteins - metabolism</subject><subject>Chikungunya virus - immunology</subject><subject>Chikungunya virus - radiation effects</subject><subject>Deinococcus - chemistry</subject><subject>Disease Models, Animal</subject><subject>Encephalitis Virus, Venezuelan Equine - immunology</subject><subject>Encephalitis Virus, Venezuelan Equine - radiation effects</subject><subject>Female</subject><subject>Gamma Rays</subject><subject>Manganese - metabolism</subject><subject>Mice, Inbred BALB C</subject><subject>Radiation-Protective Agents - metabolism</subject><subject>Vaccines, Inactivated - administration & dosage</subject><subject>Vaccines, Inactivated - immunology</subject><subject>Vaccines, Inactivated - isolation & purification</subject><subject>Viral Vaccines - administration & dosage</subject><subject>Viral Vaccines - immunology</subject><subject>Viral Vaccines - isolation & purification</subject><subject>Virus Inactivation</subject><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjssKwjAURIMgvj9BuXtpTFpiqzvxgRt34rbE9IqRNrm0tejf24WuXQ0M5zDD2FQKLoVcLh680cZYhzwUMuZC8bbtsIFM4igIlUz6bFhVDyGEiuSqx_phouKlisWAXXZonTfemGcFJwfhHAJCqm2GYHxBOb7WsAHnG8xBE5VemzvUHnROd93YstW-45BhC3kq0NVj1r3pvMLJN0dsdtift8eAntcCs5RKW-jynf6ORH-BD2H-RYk</recordid><startdate>20170622</startdate><enddate>20170622</enddate><creator>Gayen, Manoshi</creator><creator>Gupta, Paridhi</creator><creator>Morazzani, Elaine M</creator><creator>Gaidamakova, Elena K</creator><creator>Knollmann-Ritschel, Barbara</creator><creator>Daly, Michael J</creator><creator>Glass, Pamela J</creator><creator>Maheshwari, Radha K</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20170622</creationdate><title>Deinococcus Mn 2+ -peptide complex: A novel approach to alphavirus vaccine development</title><author>Gayen, Manoshi ; Gupta, Paridhi ; Morazzani, Elaine M ; Gaidamakova, Elena K ; Knollmann-Ritschel, Barbara ; Daly, Michael J ; Glass, Pamela J ; Maheshwari, Radha K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_285765703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alphavirus Infections - prevention & control</topic><topic>Animals</topic><topic>Bacterial Proteins - isolation & purification</topic><topic>Bacterial Proteins - metabolism</topic><topic>Chikungunya virus - immunology</topic><topic>Chikungunya virus - radiation effects</topic><topic>Deinococcus - chemistry</topic><topic>Disease Models, Animal</topic><topic>Encephalitis Virus, Venezuelan Equine - immunology</topic><topic>Encephalitis Virus, Venezuelan Equine - radiation effects</topic><topic>Female</topic><topic>Gamma Rays</topic><topic>Manganese - metabolism</topic><topic>Mice, Inbred BALB C</topic><topic>Radiation-Protective Agents - metabolism</topic><topic>Vaccines, Inactivated - administration & dosage</topic><topic>Vaccines, Inactivated - immunology</topic><topic>Vaccines, Inactivated - isolation & purification</topic><topic>Viral Vaccines - administration & dosage</topic><topic>Viral Vaccines - immunology</topic><topic>Viral Vaccines - isolation & purification</topic><topic>Virus Inactivation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gayen, Manoshi</creatorcontrib><creatorcontrib>Gupta, Paridhi</creatorcontrib><creatorcontrib>Morazzani, Elaine M</creatorcontrib><creatorcontrib>Gaidamakova, Elena K</creatorcontrib><creatorcontrib>Knollmann-Ritschel, Barbara</creatorcontrib><creatorcontrib>Daly, Michael J</creatorcontrib><creatorcontrib>Glass, Pamela J</creatorcontrib><creatorcontrib>Maheshwari, Radha K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gayen, Manoshi</au><au>Gupta, Paridhi</au><au>Morazzani, Elaine M</au><au>Gaidamakova, Elena K</au><au>Knollmann-Ritschel, Barbara</au><au>Daly, Michael J</au><au>Glass, Pamela J</au><au>Maheshwari, Radha K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deinococcus Mn 2+ -peptide complex: A novel approach to alphavirus vaccine development</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2017-06-22</date><risdate>2017</risdate><volume>35</volume><issue>29</issue><spage>3672</spage><pages>3672-</pages><eissn>1873-2518</eissn><abstract>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.</abstract><cop>Netherlands</cop><pmid>28576570</pmid><doi>10.1016/j.vaccine.2017.05.016</doi></addata></record> |
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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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