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Our previous studies demonstrated that the bacterial elongation factor IF-2 protein provides protection against S. suis infection in mice. On this basis, the T-cell and B-cell epitopes of IF-2 were predicted and concatenated to generate the IF2\u20131 and IF2\u20132 polypeptides. We successfully constructed IF2\u20131-T4 and IF2\u20132-T4 nanoparticles on the basis of the IF-2 protein via the T4 in vivo assembly platform. Both IF2\u20131-T4 and IF2\u20132-T4 nanoparticles exhibited superior immunoprotective efficacy compared with IF-2 in mouse models, regardless of the presence of adjuvants. Among them, IF2\u20132-T4 showed the strongest protection and demonstrated the potential to induce cross-protection against multiple S. suis serotypes, providing a promising strategy for the development of broad-spectrum S. suis vaccines. Furthermore, this study systematically evaluated the immunoprotective efficacy of a recombinant T4 phage-based vaccine in a swine model and compared the effects of intramuscular and needle-free immunization routes. Collectively, these results establish a foundation for the application of T4 nanoparticle-based vaccines in swine and offer new insights into the design of cross-protective vaccines against S. suis and other bacterial pathogens.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00464","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:15:30Z","timestamp":1785849330000},"page":"2838-2852","source":"Crossref","is-referenced-by-count":1,"title":["A Modular T4\nPhage-Based Nanoparticle Displaying Multiepitopes\nProvides Cross-Serotype Protection against\n                    <i>Streptococcus suis<\/i>\n                    in Mice and Swine"],"prefix":"10.1021","volume":"12","author":[{"given":"Guosheng","family":"Chen","sequence":"first","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiting","family":"Ni","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Guo","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Yang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengnan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]},{"name":"Wuhan Polytechnic University , , ,","place":["Wuhan, China, 430023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0082-2229","authenticated-orcid":true,"given":"Pan","family":"Tao","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, China, 430070"]},{"name":"The Cooperative Innovation Center for Sustainable Pig Production , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4622-4483","authenticated-orcid":true,"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"Huazhong Agricultural University , , , ,","place":["Wuhan, Hubei, China, 430070"]},{"name":"Huazhong Agricultural University , , ,","place":["Wuhan, China, 430070"]},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province , , ,","place":["Wuhan, Hubei, China, 430070"]},{"name":"The Cooperative Innovation Center for Sustainable Pig Production , , ,","place":["Wuhan, Hubei, China, 430070"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"issue":"1","key":"2026081410081027400_cit1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.21775\/cimb.032.473","article-title":"Recent Proceedings\non Prevalence and Pathogenesis of Streptococcus suis","volume":"32","author":"Tan","year":"2019","journal-title":"Curr. Issues Mol. Biol."},{"issue":"1","key":"2026081410081027400_cit2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s44149-025-00194-7","article-title":"Advances in Antivirulence Natural\nProducts Targeting the Suilysin of Streptococcus suis","volume":"5","author":"Wang","year":"2025","journal-title":"Anim. Dis."},{"issue":"3","key":"2026081410081027400_cit3","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S1473-3099(07)70001-4","article-title":"Streptococcus suis: An Emerging Zoonotic Pathogen","volume":"7","author":"Lun","year":"2007","journal-title":"Lancet Infect.\nDis."},{"issue":"6","key":"2026081410081027400_cit4","doi-asserted-by":"publisher","first-page":"914","DOI":"10.3201\/eid1206.051194","article-title":"Human Streptococcus suis Outbreak, Sichuan, China","volume":"12","author":"Yu","year":"2006","journal-title":"Emerg. Infect. 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Biol.\nMacromol."},{"issue":"4","key":"2026081410081027400_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/smsc.202570016","article-title":"A Modular\nBacteriophage T4 Nanoparticle Platform Enables Rapid Design of Dual\nCOVID-19-Flu Mucosal Vaccines","volume":"5","author":"Zhu","year":"2025","journal-title":"Small Sci."},{"key":"2026081410081027400_cit30","doi-asserted-by":"publisher","first-page":"721","DOI":"10.2217\/fmb-2020-0232","article-title":"Evaluation\nof the Immunoprotective Effects of IF-2 GTPase and SSU05\u20131022\nas a Candidate for a Streptococcus suis Subunit Vaccine","volume":"16","author":"Chen","year":"2021","journal-title":"Future Microbiol."},{"issue":"1","key":"2026081410081027400_cit31","doi-asserted-by":"publisher","DOI":"10.1038\/srep38061","article-title":"Immune-Responsiveness\nof CD4+ T Cells during Streptococcus suis Serotype 2 Infection","volume":"6","author":"Lecours","year":"2016","journal-title":"Sci. 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Rev. Virol."},{"issue":"6","key":"2026081410081027400_cit39","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci10060383","article-title":"Development of a Universal Multi-Epitope\nVaccine Candidate against Streptococcus suis Infections Using Immunoinformatics Approaches","volume":"10","author":"Zhang","year":"2023","journal-title":"Vet. 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Res."},{"issue":"5","key":"2026081410081027400_cit43","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11051004","article-title":"Bovine Herpesvirus-4\nBased Vaccine Provides Protective Immunity against Streptococcus suis Disease in a Rabbit Model","volume":"11","author":"Dong","year":"2023","journal-title":"Vaccines"},{"issue":"8","key":"2026081410081027400_cit44","doi-asserted-by":"publisher","DOI":"10.3390\/ani11082225","article-title":"Efficacy\nof\nSimultaneous Intradermal Vaccination of Swine against Porcine Circovirus\n2, Porcine Reproductive and Respiratory Syndrome Virus, Mycoplasma\nHyopneumoniae and Lawsonia Intracellularis","volume":"11","author":"Horsington","year":"2021","journal-title":"Animals"},{"key":"2026081410081027400_cit45","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2025.127943","article-title":"Evaluation\nof the Immunization Effects of Needle-Free Injection for Four Common\nPorcine Vaccines","volume":"68","author":"Wu","year":"2025","journal-title":"Vaccine"},{"issue":"5","key":"2026081410081027400_cit46","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.0818-9641.2004.01286.x","article-title":"Aluminium\nCompounds for Use in Vaccines","volume":"82","author":"Lindblad","year":"2004","journal-title":"Immunol. 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