{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:26:11Z","timestamp":1787009171924,"version":"build-2736575974"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001023","name":"Australian Institute of Nuclear Science and Engineering","doi-asserted-by":"publisher","award":["ALNGRA15517"],"award-info":[{"award-number":["ALNGRA15517"]}],"id":[{"id":"10.13039\/501100001023","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Government Research Training Program"},{"name":"National Health and Medical Research Council Senior Principal Research Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In recent years there has been increasing advocacy for highly immunogenic gamma-irradiated vaccines, several of which are currently in clinical or pre-clinical trials. Importantly, various methods of mathematical modelling and sterility testing are employed to ensure sterility. However, these methods are designed for materials with a low bioburden, such as food and pharmaceuticals. Consequently, current methods may not be reliable or applicable to estimate the irradiation dose required to sterilize microbiological preparations for vaccine purposes, where bioburden is deliberately high. In this study we investigated the applicability of current methods to calculate the sterilizing doses for different microbes. We generated inactivation curves that demonstrate single-hit and multiple-hit kinetics under different irradiation temperatures for high-titre preparations of pathogens with different genomic structures. Our data demonstrate that inactivation of viruses such as Influenza A virus, Zika virus, Semliki Forest virus and Newcastle Disease virus show single-hit kinetics following exposure to gamma-irradiation. In contrast, rotavirus inactivation shows multiple-hit kinetics and the sterilizing dose could not be calculated using current mathematical methods. Similarly, Streptococcus pneumoniae demonstrates multiple-hit kinetics. These variations in killing curves reveal an important gap in current mathematical formulae to determine sterility assurance levels. Here we propose a simple method to calculate the irradiation dose required for a single log10 reduction in bioburden (D10) value and sterilizing doses, incorporating both single- and multiple-hit kinetics, and taking into account the possible existence of a resistance shoulder for some pathogens following exposure to gamma-irradiation.<\/jats:p>","DOI":"10.1093\/jrr\/rraa076","type":"journal-article","created":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T07:11:49Z","timestamp":1599376309000},"page":"886-894","source":"Crossref","is-referenced-by-count":18,"title":["Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses"],"prefix":"10.1093","volume":"61","author":[{"given":"Eve V","family":"Singleton","sequence":"first","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C","family":"David","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin B","family":"Davies","sequence":"additional","affiliation":[{"name":"Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, 2234, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Hirst","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"},{"name":"Gamma Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT, 2600, Australia"},{"name":"GPN Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT, 2600, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Paton","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"},{"name":"GPN Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT, 2600, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Beard","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhid","family":"Hemmatzadeh","sequence":"additional","affiliation":[{"name":"School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, SA, 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alsharifi","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, and Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5005, Australia"},{"name":"Gamma Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT, 2600, Australia"},{"name":"GPN Vaccines Pty Ltd, Mountbatten Park, Yarralumla, ACT, 2600, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2021032415521881000_ref1","article-title":"Irradiation in the production, processing and handling of food","author":"Food and Drug Administration (FDA)","year":"2017"},{"key":"2021032415521881000_ref2","article-title":"Manual on radiation sterilization of medical and biological materials","author":"International Atomic Energy 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