{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:14:11Z","timestamp":1767183251170,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012129","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000}}],"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC2604204"],"award-info":[{"award-number":["2022YFC2604204"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFC2303503"],"award-info":[{"award-number":["2022YFC2303503"]}]},{"name":"Open Project of State Key Laboratory of Pathogen and Biosecurity","award":["SKLPBS2135"],"award-info":[{"award-number":["SKLPBS2135"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.32070136"],"award-info":[{"award-number":["No.32070136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    We recently identified two virulence-associated small open reading frames (sORF) of\n                    <jats:italic>Yersinia pestis<\/jats:italic>\n                    , named\n                    <jats:italic>yp1<\/jats:italic>\n                    and\n                    <jats:italic>yp2<\/jats:italic>\n                    , and null mutants of each individual genes were highly attenuated in virulence. Plague vaccine strain EV76 is known for strong reactogenicity, making it not suitable for use in humans. To improve the immune safety of EV76, three mutant strains of EV76, \u0394\n                    <jats:italic>yp1<\/jats:italic>\n                    , \u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    , and \u0394\n                    <jats:italic>yp1&amp;yp2<\/jats:italic>\n                    were constructed and their virulence attenuation, immunogenicity, and protective efficacy in mice were evaluated. All mutant strains were attenuated by the subcutaneous (\n                    <jats:italic>s<\/jats:italic>\n                    .\n                    <jats:italic>c<\/jats:italic>\n                    .) route and exhibited more rapid clearance in tissues than the parental strain EV76. Under iron overload conditions, only the mice infected with EV76\u0394\n                    <jats:italic>yp1<\/jats:italic>\n                    survived, accompanied by less draining lymph nodes damage than those infected by EV76. Analysis of cytokines secreted by splenocytes of immunized mice found that EV76\u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    induced higher secretion of multiple cytokines including TNF-\u03b1, IL-2, and IL-12p70 than EV76. On day 42, EV76\u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    or EV76\u0394\n                    <jats:italic>yp1&amp;yp2<\/jats:italic>\n                    immunized mice exhibited similar protective efficacy as EV76 when exposed to\n                    <jats:italic>Y<\/jats:italic>\n                    .\n                    <jats:italic>pestis<\/jats:italic>\n                    201, both via\n                    <jats:italic>s<\/jats:italic>\n                    .\n                    <jats:italic>c<\/jats:italic>\n                    . or intranasal (\n                    <jats:italic>i<\/jats:italic>\n                    .\n                    <jats:italic>n<\/jats:italic>\n                    .) routes of administration. Moreover, when exposed to 200\u2013400 LD\n                    <jats:sub>50<\/jats:sub>\n                    <jats:italic>Y<\/jats:italic>\n                    .\n                    <jats:italic>pestis<\/jats:italic>\n                    strain 201\u0394\n                    <jats:italic>caf1<\/jats:italic>\n                    (non-encapsulated\n                    <jats:italic>Y<\/jats:italic>\n                    .\n                    <jats:italic>pestis<\/jats:italic>\n                    ), EV76\u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    or EV76\u0394\n                    <jats:italic>yp1&amp;yp2<\/jats:italic>\n                    are able to afford about 50% protection to\n                    <jats:italic>i<\/jats:italic>\n                    .\n                    <jats:italic>n<\/jats:italic>\n                    . challenges, significantly better than the protection afforded by EV76. On 120 day, mice immunized with EV76\u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    or EV76\u0394\n                    <jats:italic>yp1&amp;yp2<\/jats:italic>\n                    cleared the\n                    <jats:italic>i<\/jats:italic>\n                    .\n                    <jats:italic>n<\/jats:italic>\n                    . challenge of\n                    <jats:italic>Y<\/jats:italic>\n                    .\n                    <jats:italic>pestis<\/jats:italic>\n                    201-\n                    <jats:italic>lux<\/jats:italic>\n                    as quickly as those immunized with EV76, demonstrating 90\u2013100% protection. Our results demonstrated that deletion of the\n                    <jats:italic>yp2<\/jats:italic>\n                    gene is an effective strategy to attenuate virulence of\n                    <jats:italic>Y<\/jats:italic>\n                    .\n                    <jats:italic>pestis<\/jats:italic>\n                    EV76 while improving immunogenicity. Furthermore, EV76\u0394\n                    <jats:italic>yp2<\/jats:italic>\n                    is a promising candidate for conferring protection against the pneumonic and bubonic forms of plague.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012129","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T14:21:25Z","timestamp":1711635685000},"page":"e1012129","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel sORF gene mutant strain of Yersinia pestis vaccine EV76 offers enhanced safety and improved protection against plague"],"prefix":"10.1371","volume":"20","author":[{"given":"Xiao","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youquan","family":"Xin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehui","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gengshan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajun","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruifu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0037-1616","authenticated-orcid":true,"given":"Zongmin","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"issue":"1","key":"ppat.1012129.ref001","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1128\/CMR.10.1.35","article-title":"Yersinia pestis\u2014etiologic agent of plague","volume":"10","author":"RD Perry","year":"1997","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1012129.ref002","first-page":"34","article-title":"Yersinia pestis: the Natural History of Plague.","author":"R Barbieri","year":"2020","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"ppat.1012129.ref003","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jobb.2020.02.001","article-title":"Deliberate release: Plague\u2014A review.","volume":"2","author":"I Ansari","year":"2020","journal-title":"J Biosaf Biosecur"},{"key":"ppat.1012129.ref004","unstructured":"Plague outbreak situation report. 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