A novel gamma radiation-inactivated sabin-based polio vaccine
A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. O...
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creator | Tobin, Gregory J Tobin, John K Gaidamakova, Elena K Wiggins, Taralyn J Bushnell, Ruth V Lee, Wai-Ming Matrosova, Vera Y Dollery, Stephen J Meeks, Heather N Kouiavskaia, Diana Chumakov, Konstantin Daly, Michael J |
description | A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest. |
doi_str_mv | 10.1371/journal.pone.0228006 |
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However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0228006</identifier><identifier>PMID: 31999745</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antibodies, Neutralizing - immunology ; Antigenic determinants ; Antioxidants ; Antioxidants (Nutrients) ; Backup software ; Bacteria ; Biological products ; Biology and Life Sciences ; Biosecurity ; Deactivation ; Disease eradication ; Drug dosages ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Food ; Formaldehyde ; Gamma radiation ; Gamma Rays ; Genome, Viral ; Genomes ; Genomics ; Health sciences ; HeLa Cells ; Humans ; I.R. radiation ; Immune response ; Immunity ; Immunogenicity ; Immunotherapy ; Inactivation ; Intestine ; Ionizing radiation ; Irradiation ; Manufacturing ; Medicine and Health Sciences ; Methods ; Military medicine ; Neurovirulence ; Neutralizing ; Oxidative Stress ; Pathology ; Peptides ; Peptides - blood ; Physical Sciences ; Poliomyelitis ; Poliovirus - genetics ; Poliovirus - immunology ; Poliovirus - pathogenicity ; Poliovirus - ultrastructure ; Poliovirus Vaccine, Inactivated - immunology ; Poliovirus Vaccine, Oral - immunology ; Production management ; Production methods ; Proteins ; Radiation ; Radiation (Physics) ; Radiation damage ; Radiation effects ; Radiation exposure ; Rats, Wistar ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Strains (organisms) ; Supervision ; Time ; Vaccines ; Viral Proteins - metabolism ; Viruses ; γ Radiation</subject><ispartof>PloS one, 2020-01, Vol.15 (1), p.e0228006-e0228006</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5b671d7c16edc49401ced737b3877a3130a4615fdd3a6ca24a357099176c1c983</citedby><cites>FETCH-LOGICAL-c692t-5b671d7c16edc49401ced737b3877a3130a4615fdd3a6ca24a357099176c1c983</cites><orcidid>0000-0002-1712-3811</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991977/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991977/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31999745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Alsharifi, Mohammed</contributor><creatorcontrib>Tobin, Gregory J</creatorcontrib><creatorcontrib>Tobin, John K</creatorcontrib><creatorcontrib>Gaidamakova, Elena K</creatorcontrib><creatorcontrib>Wiggins, Taralyn J</creatorcontrib><creatorcontrib>Bushnell, Ruth V</creatorcontrib><creatorcontrib>Lee, Wai-Ming</creatorcontrib><creatorcontrib>Matrosova, Vera Y</creatorcontrib><creatorcontrib>Dollery, Stephen J</creatorcontrib><creatorcontrib>Meeks, Heather N</creatorcontrib><creatorcontrib>Kouiavskaia, Diana</creatorcontrib><creatorcontrib>Chumakov, Konstantin</creatorcontrib><creatorcontrib>Daly, Michael J</creatorcontrib><title>A novel gamma radiation-inactivated sabin-based polio vaccine</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antigenic determinants</subject><subject>Antioxidants</subject><subject>Antioxidants (Nutrients)</subject><subject>Backup software</subject><subject>Bacteria</subject><subject>Biological products</subject><subject>Biology and Life Sciences</subject><subject>Biosecurity</subject><subject>Deactivation</subject><subject>Disease eradication</subject><subject>Drug dosages</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes</subject><subject>Food</subject><subject>Formaldehyde</subject><subject>Gamma radiation</subject><subject>Gamma Rays</subject><subject>Genome, Viral</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health sciences</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>I.R. radiation</subject><subject>Immune response</subject><subject>Immunity</subject><subject>Immunogenicity</subject><subject>Immunotherapy</subject><subject>Inactivation</subject><subject>Intestine</subject><subject>Ionizing radiation</subject><subject>Irradiation</subject><subject>Manufacturing</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Military medicine</subject><subject>Neurovirulence</subject><subject>Neutralizing</subject><subject>Oxidative Stress</subject><subject>Pathology</subject><subject>Peptides</subject><subject>Peptides - blood</subject><subject>Physical Sciences</subject><subject>Poliomyelitis</subject><subject>Poliovirus - genetics</subject><subject>Poliovirus - immunology</subject><subject>Poliovirus - pathogenicity</subject><subject>Poliovirus - ultrastructure</subject><subject>Poliovirus Vaccine, Inactivated - immunology</subject><subject>Poliovirus Vaccine, Oral - immunology</subject><subject>Production management</subject><subject>Production methods</subject><subject>Proteins</subject><subject>Radiation</subject><subject>Radiation (Physics)</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Radiation exposure</subject><subject>Rats, Wistar</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Strains (organisms)</subject><subject>Supervision</subject><subject>Time</subject><subject>Vaccines</subject><subject>Viral Proteins - metabolism</subject><subject>Viruses</subject><subject>γ Radiation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QHBNGLjkmTJs2FwrD4MbCw4NdtOE3SmQxpMtu0g_57U6e7TGUvJBcJyXPe85E3y55jtMSE43e7MHQe3HIfvFmioqgQYg-ycyxIkbMCkYcn57PsSYw7hEpSMfY4OyNYCMFpeZ69Xy18OBi32EDbwqIDbaG3wefWg-rtAXqjFxFq6_MaYjrvg7NhcQClrDdPs0cNuGieTftF9uPTx--XX_Kr68_ry9VVrpgo-rysGceaK8yMVlRQhJXRnPCaVJwDwQQBZbhstCbAFBQUSMmREJgzhZWoyEX28qi7dyHKqfMoC0IrXtFKiESsj4QOsJP7zrbQ_ZYBrPx7EbqNhK63yhnJVUERkELrRtMqjYLXhmmDRWWUpoQnrQ9TtqFuU8XG9x24mej8xdut3ISDZKlkwUeBN5NAF24GE3vZ2qiMc-BNGMa6S4REhcoRffUPen93E7WB1ID1TUh51SgqVwwXvOSUkEQt76HS0qa1Ktmksel-FvB2FpCY3vzqNzDEKNffvv4_e_1zzr4-YbcGXL-NwQ2jseIcpEdQdSHGzjR3Q8ZIji6_nYYcXS4nl6ewF6cfdBd0a2vyB9NE9ZI</recordid><startdate>20200130</startdate><enddate>20200130</enddate><creator>Tobin, Gregory J</creator><creator>Tobin, John K</creator><creator>Gaidamakova, Elena K</creator><creator>Wiggins, Taralyn J</creator><creator>Bushnell, Ruth V</creator><creator>Lee, Wai-Ming</creator><creator>Matrosova, Vera Y</creator><creator>Dollery, Stephen J</creator><creator>Meeks, Heather N</creator><creator>Kouiavskaia, Diana</creator><creator>Chumakov, Konstantin</creator><creator>Daly, Michael J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1712-3811</orcidid></search><sort><creationdate>20200130</creationdate><title>A novel gamma radiation-inactivated sabin-based polio vaccine</title><author>Tobin, Gregory J ; Tobin, John K ; Gaidamakova, Elena K ; Wiggins, Taralyn J ; Bushnell, Ruth V ; Lee, Wai-Ming ; Matrosova, Vera Y ; Dollery, Stephen J ; Meeks, Heather N ; Kouiavskaia, Diana ; Chumakov, Konstantin ; Daly, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5b671d7c16edc49401ced737b3877a3130a4615fdd3a6ca24a357099176c1c983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Neutralizing - 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blood</topic><topic>Physical Sciences</topic><topic>Poliomyelitis</topic><topic>Poliovirus - genetics</topic><topic>Poliovirus - immunology</topic><topic>Poliovirus - pathogenicity</topic><topic>Poliovirus - ultrastructure</topic><topic>Poliovirus Vaccine, Inactivated - immunology</topic><topic>Poliovirus Vaccine, Oral - immunology</topic><topic>Production management</topic><topic>Production methods</topic><topic>Proteins</topic><topic>Radiation</topic><topic>Radiation (Physics)</topic><topic>Radiation damage</topic><topic>Radiation effects</topic><topic>Radiation exposure</topic><topic>Rats, Wistar</topic><topic>Research and Analysis Methods</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Strains (organisms)</topic><topic>Supervision</topic><topic>Time</topic><topic>Vaccines</topic><topic>Viral Proteins - metabolism</topic><topic>Viruses</topic><topic>γ Radiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tobin, Gregory J</creatorcontrib><creatorcontrib>Tobin, John K</creatorcontrib><creatorcontrib>Gaidamakova, Elena K</creatorcontrib><creatorcontrib>Wiggins, Taralyn J</creatorcontrib><creatorcontrib>Bushnell, Ruth V</creatorcontrib><creatorcontrib>Lee, Wai-Ming</creatorcontrib><creatorcontrib>Matrosova, Vera Y</creatorcontrib><creatorcontrib>Dollery, Stephen J</creatorcontrib><creatorcontrib>Meeks, Heather N</creatorcontrib><creatorcontrib>Kouiavskaia, Diana</creatorcontrib><creatorcontrib>Chumakov, Konstantin</creatorcontrib><creatorcontrib>Daly, Michael J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tobin, Gregory J</au><au>Tobin, John K</au><au>Gaidamakova, Elena K</au><au>Wiggins, Taralyn J</au><au>Bushnell, Ruth V</au><au>Lee, Wai-Ming</au><au>Matrosova, Vera Y</au><au>Dollery, Stephen J</au><au>Meeks, Heather N</au><au>Kouiavskaia, Diana</au><au>Chumakov, Konstantin</au><au>Daly, Michael J</au><au>Alsharifi, Mohammed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel gamma radiation-inactivated sabin-based polio vaccine</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-01-30</date><risdate>2020</risdate><volume>15</volume><issue>1</issue><spage>e0228006</spage><epage>e0228006</epage><pages>e0228006-e0228006</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31999745</pmid><doi>10.1371/journal.pone.0228006</doi><orcidid>https://orcid.org/0000-0002-1712-3811</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2020-01, Vol.15 (1), p.e0228006-e0228006 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2348784899 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Animals Antibodies Antibodies, Neutralizing - immunology Antigenic determinants Antioxidants Antioxidants (Nutrients) Backup software Bacteria Biological products Biology and Life Sciences Biosecurity Deactivation Disease eradication Drug dosages Enzyme-Linked Immunosorbent Assay Epitopes Food Formaldehyde Gamma radiation Gamma Rays Genome, Viral Genomes Genomics Health sciences HeLa Cells Humans I.R. radiation Immune response Immunity Immunogenicity Immunotherapy Inactivation Intestine Ionizing radiation Irradiation Manufacturing Medicine and Health Sciences Methods Military medicine Neurovirulence Neutralizing Oxidative Stress Pathology Peptides Peptides - blood Physical Sciences Poliomyelitis Poliovirus - genetics Poliovirus - immunology Poliovirus - pathogenicity Poliovirus - ultrastructure Poliovirus Vaccine, Inactivated - immunology Poliovirus Vaccine, Oral - immunology Production management Production methods Proteins Radiation Radiation (Physics) Radiation damage Radiation effects Radiation exposure Rats, Wistar Research and Analysis Methods Ribonucleic acid RNA Strains (organisms) Supervision Time Vaccines Viral Proteins - metabolism Viruses γ Radiation |
title | A novel gamma radiation-inactivated sabin-based polio vaccine |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T13%3A11%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20gamma%20radiation-inactivated%20sabin-based%20polio%20vaccine&rft.jtitle=PloS%20one&rft.au=Tobin,%20Gregory%20J&rft.date=2020-01-30&rft.volume=15&rft.issue=1&rft.spage=e0228006&rft.epage=e0228006&rft.pages=e0228006-e0228006&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0228006&rft_dat=%3Cgale_plos_%3EA612757433%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2348784899&rft_id=info:pmid/31999745&rft_galeid=A612757433&rft_doaj_id=oai_doaj_org_article_7c240a32ddfd483197be6de198ecd437&rfr_iscdi=true |