{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:02:41Z","timestamp":1785409361066,"version":"3.56.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The segmented genome of live-attenuated rotavirus (RV) vaccines provides an ideal platform for developing multivalent vaccines against enteric pathogens. Here, we engineered the commercial human RV vaccine strain LLR as a vector to deliver\n                      <jats:italic toggle=\"yes\">Clostridium perfringens<\/jats:italic>\n                      alpha-toxin (CPA), a critical virulence factor associated with gastroenteritis. A screen of four 2A peptide sequences identified that porcine teschovirus-1 2A (P2A) preceded by an N-terminal GSG spacer enabled optimal cleavage and antigen expression. In mice, the resulting recombinant virus elicited potent systemic antibody responses against both RV and CPA following oral administration. When tested in a maternal immunization model, intramuscular immunization of cows generated high titers of neutralizing antibodies in colostrum, demonstrating its potential utility for passive immunization. By integrating a key bacterial antigen into a licensed RV vaccine backbone, we establish a versatile strategy to combat viral-bacterial co-infections and polymicrobial enteric diseases, offering a promising new approach to reduce the global burden of diarrheal mortality.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The lack of vaccines targeting polymicrobial enteric infections represents a critical gap in the fight against diarrheal diseases, a leading cause of infant mortality worldwide. To bridge this gap, we engineered a novel bivalent vaccine designed to provide dual protection against rotavirus and\n                        <jats:italic toggle=\"yes\">Clostridium perfringens<\/jats:italic>\n                        alpha-toxin (CPA)-mediated disease. Leveraging an enhanced reverse genetics system, we successfully utilized the commercialized rotavirus vaccine strain LLR as a viral vector to express the key\n                        <jats:italic toggle=\"yes\">C. perfringens<\/jats:italic>\n                        virulence factor, CPA. This strategy not only offers a path to broader protection against diarrheal disease but also establishes a versatile platform for developing vaccines against other viral-bacterial co-infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00178-26","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:00:24Z","timestamp":1774530024000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["An oral rotavirus-vectored vaccine confers protection against\n                    <i>Clostridium perfringens<\/i>\n                    and rotavirus"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-7924","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]},{"id":[{"id":"https:\/\/ror.org\/030jxf285","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University","place":["Daqing, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2178-855X","authenticated-orcid":false,"given":"Jitao","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]},{"id":[{"id":"https:\/\/ror.org\/0313jb750","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Western Agriculture, Chinese Academy of Agricultural Sciences","place":["Changji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hechun","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]},{"id":[{"id":"https:\/\/ror.org\/030jxf285","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University","place":["Daqing, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Jia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuanhao","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Xiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songkang","family":"Qin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Han","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binxin","family":"Yao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-6718","authenticated-orcid":true,"given":"Xin","family":"Yin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034e92n57","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences","place":["Harbin, China"]},{"id":[{"id":"https:\/\/ror.org\/030jxf285","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University","place":["Daqing, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-3763","authenticated-orcid":true,"given":"Dongbo","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/030jxf285","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University","place":["Daqing, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00794-x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13099-016-0141-1"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.1382"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02200-20"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070955"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.713485"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201102-0271OC"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15856"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34005"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.gpp3-0003-2017"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1013"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1754714"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11040339"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2018.1960"},{"key":"e_1_3_5_16_2","unstructured":"Batch release of biological products. 2025. National Institutes for Food and Drug Control. Available from: https:\/\/bio.nifdc.org.cn\/pqf\/search.do"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.10.036"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2015.64"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2018.04.011"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/anae.1999.0191"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci11080381"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12198"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2019.1582975"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.04.016"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virs.2024.09.010"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2025.02.005"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2214421120"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2004.02.007"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02123694"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-016-0157-2"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep16273"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt957"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2015.1008351"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200900134"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13030212"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.52.1.333"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00276-22"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8090266"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00209-18"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6702a1"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02770"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.864377"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.67.5.2448-2455.1993"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1367385"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1748171"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.05.059"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00178-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00178-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:04:04Z","timestamp":1776776644000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00178-26"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,21]]}},"alternative-id":["10.1128\/jvi.00178-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00178-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"2026-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00178-26"}}