{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:03:39Z","timestamp":1789668219399,"version":"4.0.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Acinetobacter baumannii<\/jats:italic> causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant <jats:italic>A. baumannii<\/jats:italic> at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing \u03b3-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection <jats:italic>via<\/jats:italic> the passive immunization of neutropenic mice.<\/jats:p>","DOI":"10.3389\/fimmu.2022.941010","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T05:03:00Z","timestamp":1664254980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Whole-cell vaccine candidates induce a protective response against virulent Acinetobacter baumannii"],"prefix":"10.3389","volume":"13","author":[{"given":"Stephen J.","family":"Dollery","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel V.","family":"Zurawski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth V.","family":"Bushnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Tobin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taralyn J.","family":"Wiggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"MacLeod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi J. P. E. R.","family":"Tasker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonas A.","family":"Alamneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Abu-Taleb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Czintos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariel G.","family":"Escatte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather N.","family":"Meeks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Tobin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"B1","unstructured":"Priority pathogens list for R&D of new antibiotics2017"},{"key":"B2","volume-title":"Antibiotic resistance threats in the united states, 2019","year":"2019"},{"key":"B3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1086\/653120","article-title":"Treatment of acinetobacter infections","volume":"51","author":"Fishbain","year":"2010","journal-title":"Clin Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"100077","DOI":"10.1016\/j.infpip.2020.100077","article-title":"Control and management of multidrug resistant acinetobacter baumannii: A review of the evidence and proposal of novel approaches","volume":"2","author":"Weinberg","year":"2020","journal-title":"Infect Prev practice."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000052","article-title":"Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant acinetobacter baumannii global clone 1","volume":"2","author":"Holt","year":"2016","journal-title":"Microb Genomics"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-07","article-title":"Acinetobacter baumannii: emergence of a successful pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin Microbiol Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01601","article-title":"The mechanisms of disease caused by acinetobacter baumannii","volume":"10","author":"Morris","year":"2019","journal-title":"Front Microbiol"},{"key":"B8","article-title":"Acinetobacter baumannii in casualties returning from Afghanistan","volume":"22","author":"Stuart","year":"2007","journal-title":"Can J infection control"},{"key":"B9","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/nrd3957-c1","article-title":"The value of single-pathogen antibacterial agents","volume":"12","author":"Spellberg","year":"2013","journal-title":"Nat Rev Drug discov"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10081006","article-title":"Acinetobacter baumannii infections in times of COVID-19 pandemic","volume":"10","author":"Rangel","year":"2021","journal-title":"Pathog (Basel Switzerland)."},{"key":"B12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3855\/jidc.13545","article-title":"Clonal dispersion of acinetobacter baumannii in an intensive care unit designed to patients COVID-19","volume":"15","author":"Dur\u00e1n-Manuel","year":"2021","journal-title":"J infection developing countries."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18084358","article-title":"Co-Infections in critically ill patients with or without COVID-19: A comparison of clinical microbial culture findings","volume":"18","author":"Cultrera","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s13205-022-03148-9","article-title":"Vaccine development to control the rising scourge of antibiotic-resistant acinetobacter baumannii: A systematic review","volume":"12","author":"Singh","year":"2022","journal-title":"3 Biotech."},{"key":"B15","doi-asserted-by":"publisher","first-page":"570","DOI":"10.3390\/vaccines9060570","article-title":"Mapping global prevalence of acinetobacter baumannii and recent vaccine development to tackle it","volume":"9","author":"Ma","year":"2021","journal-title":"Vaccines (Basel)."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.3390\/pathogens9121066","article-title":"Recent advances in the pursuit of an effective acinetobacter baumannii vaccine","volume":"9","author":"Gellings","year":"2020","journal-title":"Pathog (Basel Switzerland)."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.666742","article-title":"Designing multi-antigen vaccines against acinetobacter baumannii using systemic approaches","volume":"12","author":"McConnell","year":"2021","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"897","DOI":"10.2174\/1389201014666131226123511","article-title":"First steps towards a vaccine against acinetobacter baumannii","volume":"14","author":"Garcia-Quintanilla","year":"2013","journal-title":"Curr Pharm Biotechnol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vaccine.2010.10.052","article-title":"Active and passive immunization against acinetobacter baumannii using an inactivated whole cell vaccine","volume":"29","author":"McConnell","year":"2010","journal-title":"Vaccine"},{"key":"B20","doi-asserted-by":"publisher","first-page":"22332","DOI":"10.1038\/srep22332","article-title":"An inactivated antibiotic-exposed whole-cell vaccine enhances bactericidal activities against multidrug-resistant acinetobacter baumannii","volume":"6","author":"Shu","year":"2016","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.02.083","article-title":"Intranasal immunization protects against acinetobacter baumannii-associated pneumonia in mice","volume":"33","author":"KuoLee","year":"2015","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1780091","article-title":"Characterization of humoral and cellular immune features of gamma-irradiated influenza vaccine","volume":"17","author":"Chen","year":"2021","journal-title":"Hum Vaccines immunother"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nm1456","article-title":"A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines","volume":"12","author":"Moghaddam","year":"2006","journal-title":"Nat Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9020096","article-title":"Radiation-inactivated acinetobacter baumannii vaccine candidates","volume":"9","author":"Dollery","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e0228006","DOI":"10.1371\/journal.pone.0228006","article-title":"A novel gamma radiation-inactivated sabin-based polio vaccine","volume":"15","author":"Tobin","year":"2020","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.05.016","article-title":"Deinococcus Mn(2+)-peptide complex: A novel approach to alphavirus vaccine development","volume":"35","author":"Gayen","year":"2017","journal-title":"Vaccine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.05.011","article-title":"Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio- protective Mn2+-peptide complex from deinococcus","volume":"12","author":"Gaidamakova","year":"2012","journal-title":"Cell Host Microbe"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0339421","DOI":"10.1128\/mbio.03394-21","article-title":"Small-molecule Mn antioxidants in caenorhabditis elegans and deinococcus radiodurans supplant MnSOD enzymes during aging and irradiation","volume":"13","author":"Gaidamakova","year":"2022","journal-title":"mBio"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5093","article-title":"Manganese complexes: Diverse metabolic routes to oxidative stress resistance in prokaryotes and yeast","volume":"19","author":"Culotta","year":"2013","journal-title":"Antioxid Redox Signaling"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2073","article-title":"A new perspective on radiation resistance based on deinococcus radiodurans","volume":"7","author":"Daly","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713608114","article-title":"Across the tree of life, radiation resistance is governed by antioxidant Mn(2+), gauged by paramagnetic resonance","volume":"114","author":"Sharma","year":"2017","journal-title":"Proc Natl Acad Sci United States America."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e12570","DOI":"10.1371\/journal.pone.0012570","article-title":"Small-molecule antioxidant proteome-shields in deinococcus radiodurans","volume":"5","author":"Daly","year":"2010","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"833","DOI":"10.3390\/vaccines10060833","article-title":"Select whole-cell biofilm-based immunogens protect against a virulent staphylococcus isolate in a stringent implant model of infection","volume":"10","author":"Dollery","year":"2022","journal-title":"Vaccines (Basel)."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01076-14","article-title":"AB5075, a highly virulent isolate of <span class=\"named-content genus-species\" id=\"named-content-1\">Acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments","volume":"5","author":"Jacobs","year":"2014","journal-title":"mBio"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01239-17","article-title":"SPR741, an antibiotic adjuvant, potentiates the in vitro and In vivo activity of rifampin against clinically relevant extensively drug-resistant acinetobacter baumannii","volume":"61","author":"Zurawski","year":"2017","journal-title":"Antimicrob Agents chemother"},{"key":"B36","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1186\/s12864-015-1608-z","article-title":"Quantitative proteomic analysis of host\u2013pathogen interactions: A study of acinetobacter baumannii responses to host airways","volume":"16","author":"M\u00e9ndez","year":"2015","journal-title":"BMC Genomics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1089\/mdr.2016.0190","article-title":"Distinct genetic diversity of carbapenem-resistant acinetobacter baumannii from Colombian hospitals","volume":"24","author":"Correa","year":"2018","journal-title":"Microb Drug resistance (Larchmont NY)."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00586-19","article-title":"Clearance of staphylococcus aureus from in vivo models of chronic infection by immunization requires both planktonic and biofilm antigens","volume":"88","author":"Harro","year":"2019","journal-title":"Infect Immun"},{"key":"B39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/1471-2180-10-173","article-title":"Genetic variation in staphylococcus aureus surface and immune evasion genes is lineage associated: Implications for vaccine design and host-pathogen interactions","volume":"10","author":"McCarthy","year":"2010","journal-title":"BMC Microbiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.705360","article-title":"Staphylococcus aureus vaccine research and development: The past, present and future, including novel therapeutic strategies","volume":"12","author":"Clegg","year":"2021","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"15480","DOI":"10.1038\/ncomms15480","article-title":"Design of live attenuated bacterial vaccines based on d-glutamate auxotrophy","volume":"8","author":"Cabral","year":"2017","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01379","article-title":"Anti-outer membrane vesicle antibodies increase antibiotic sensitivity of pan-Drug-Resistant acinetobacter baumannii","volume":"10","author":"Huang","year":"2019","journal-title":"Front Microbiol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"4416","DOI":"10.3390\/ijms21124416","article-title":"OMV vaccines and the role of TLR agonists in immune response","volume":"21","author":"Mancini","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.06.001","article-title":"Outer membrane vesicles as an acellular vaccine against acinetobacter baumannii","volume":"29","author":"McConnell","year":"2011","journal-title":"Vaccine"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.1.147","article-title":"Antiseptics and disinfectants: Activity, action, and resistance","volume":"12","author":"McDonnell","year":"1999","journal-title":"Clin Microbiol Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103185","article-title":"Accumulation of Mn(II) in deinococcus radiodurans facilitates gamma-radiation resistance","volume":"306","author":"Daly","year":"2004","journal-title":"Sci (New York NY)."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050092","article-title":"Protein oxidation implicated as the primary determinant of bacterial radioresistance","volume":"5","author":"Daly","year":"2007","journal-title":"PloS Biol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/ismej.2007.116","article-title":"Protein oxidation: Key to bacterial desiccation resistance","volume":"2","author":"Fredrickson","year":"2008","journal-title":"ISME J"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.941010\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T05:03:09Z","timestamp":1664254989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.941010\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2022.941010"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.941010","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]},"article-number":"941010"}}