{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:01:42Z","timestamp":1785243702744,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Agricultural Science and Technology Innovation Program","award":["T2023331"],"award-info":[{"award-number":["T2023331"]}]},{"name":"SAAS Program for Excellent Research Team","award":["[2022]012"],"award-info":[{"award-number":["[2022]012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Porcine epidemic diarrhea virus (PEDV) is a major enteric coronavirus that causes severe economic losses to the global swine industry. Current vaccines suffer from weak immunogenicity, insufficient mucosal immunity, and a short duration of protection. Nanoparticle delivery systems have emerged as a promising strategy for next-generation vaccine development. In the present study, we constructed an S1-Ferritin nanoparticle vaccine using the SpyTag-SpyCatcher modular conjugation system. The morphology, particle size, and uniformity of the nanoparticle vaccine were systematically characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After two immunizations, the S-Ferritin nanoparticle vaccine elicited potent humoral and cellular immune responses in both mice and piglets. In piglets, at 2 weeks post booster vaccination, PEDV-specific serum IgG endpoint titers peaked at 1:2560, virus-neutralizing antibody titers reached 1:256 against the JS-2\/2015 strain, and serum IFN-\u03b3 levels reached 274 pg\/mL. All these immunological indicators were significantly higher than those observed in the PEDV-inactivated whole-virus vaccine group. Furthermore, challenge tests showed that the S1-Ferritin nanoparticle vaccine provided complete protection against PEDV infection and significantly reduced the severity of diarrhea and intestinal damage in piglets after challenge. These findings suggest that the S1-Ferritin nanoparticle vaccine constitutes a promising candidate against PEDV infection, though our study is only a preliminary step and subsequent field trials in pigs are still required.<\/jats:p>","DOI":"10.3390\/biom16081090","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanoparticle Vaccine Based on S1 Domain of Porcine Epidemic Diarrhea Virus Elicits Protective Immune Responses in Mice and Pigs"],"prefix":"10.3390","volume":"16","author":[{"given":"Pan","family":"Tang","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhui","family":"Cui","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tao","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shi","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilei","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huili","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shi, Y., Li, B.Q., Tao, J., Cheng, J.H., and Liu, H.L. (2021). The Complex Co-infections of Multiple Porcine Diarrhea Viruses in Local Area Based on the Luminex xTAG Multiplex Detection Method. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.602866"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ibrahim, Y.M., Liu, C., Yu, Y.D., Yang, L., Chen, Q.L., Ma, W.J., Werid, G.M., Li, S.M., Luo, J., and Gao, S.B. (2026). Swine Enteric Coronaviruses: An Updated Overview of Epidemiology, Diagnosis, Prevention, and Control. Animals, 16.","DOI":"10.3390\/ani16030458"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"msad052","DOI":"10.1093\/molbev\/msad052","article-title":"Global Dynamics of Porcine Enteric Coronavirus PEDV Epidemiology, Evolution, and Transmission","volume":"40","author":"Zhang","year":"2023","journal-title":"Mol. Biol. Evol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s11671-025-04220-y","article-title":"Advances in porcine epidemic diarrhea virus research: Genome, epidemiology, vaccines, and detection methods","volume":"20","author":"Zhuang","year":"2025","journal-title":"Discov. Nano"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lu, X., Chen, C., Wang, Z.X., and Zhang, A.D. (2025). Isolation and Characterization of Porcine Epidemic Diarrhea Virus G2c Strains Circulating in China from 2021 to 2024. Vet. Sci., 12.","DOI":"10.3390\/vetsci12050444"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, Z.B., Yang, K., Bi, M.F., Li, K.J., Wang, W., Song, Y., Pan, X.M., Li, T.Z., and Mo, X.B. (2025). Molecular characteristics and potential antigenic epitope analysis of porcine epidemic diarrhea virus in China from 2022 to 2025. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1667063"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fu, Y.J., Wang, Y.C., Dai, L.L., Cheng, B.M., Xiao, S.Q., and Yin, Y.P. (2025). Evolutionary dynamics and antigenic diversity of porcine epidemic diarrhea virus (PEDV) in China: Phylogenetic and recombination analyses based on large-scale S gene sequences. BMC Vet. Res., 21.","DOI":"10.1186\/s12917-025-04873-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00705-025-06308-3","article-title":"Epidemiological investigation, isolation, and pathogenicity of porcine epidemic diarrhea virus subtype G2c in Sichuan province","volume":"170","author":"Wang","year":"2025","journal-title":"Arch. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e02165-24","DOI":"10.1128\/jvi.02165-24","article-title":"Spike gene variability in porcine epidemic diarrhea virus as a determinant for virulence","volume":"99","author":"Li","year":"2025","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Luo, H.J., Liang, Z.P., Lin, J.J., Wang, Y.Q., Liu, Y.Y., Mei, K., Zhao, M.M., and Huang, S.J. (2024). Research progress of porcine epidemic diarrhea virus S protein. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1396894"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Park, J.E. (2024). Porcine Epidemic Diarrhea: Insights and Progress on Vaccines. Vaccines, 12.","DOI":"10.20944\/preprints202401.1467.v1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125597","DOI":"10.1016\/j.ijpharm.2025.125597","article-title":"Self-Assembling protein nanoparticle platform for multivalent antigen delivery in vaccine development","volume":"676","author":"Wu","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature12202","article-title":"Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies","volume":"499","author":"Kanekiyo","year":"2013","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1021\/acsnano.0c08379","article-title":"Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates","volume":"15","author":"Kang","year":"2021","journal-title":"ACS Nano"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136653","DOI":"10.1172\/jci.insight.136653","article-title":"Self-assembling influenza nanoparticle vaccines drive extended germinal center activity and memory B cell maturation","volume":"5","author":"Kelly","year":"2020","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41392-023-01425-4","article-title":"An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41565-020-0648-y","article-title":"Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B","volume":"15","author":"Wang","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"ref_18","first-page":"1304","article-title":"A Nanoparticle-Based Hepatitis C Virus Vaccine with Enhanced Potency","volume":"221","author":"Yan","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Peng, Y., Zong, Y.J., Wang, D.F., Chen, J.B., Chen, Z.S., Peng, F.J., and Liu, Z.J. (2023). Current drugs for HIV-1: From challenges to potential in HIV\/AIDS. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1294966"},{"key":"ref_20","first-page":"576","article-title":"Nanoparticle cancer vaccines: Design considerations and recent advances","volume":"15","author":"Liu","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tang, P., Cui, E.H., Cheng, J.H., Li, B.Q., Tao, J., Shi, Y., Jiao, J.J., Du, E.Q., Wang, J.Y., and Liu, H.L. (2024). A ferritin nanoparticle vaccine based on the hemagglutinin extracellular domain of swine influenza A (H1N1) virus elicits protective immune responses in mice and pigs. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1361323"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhong, D.L., Lu, Z.H., Xia, Y., Wu, H.X., Zhang, X.Y., Li, M.Z., Song, X., Wang, Y.J., Moon, A., and Qiu, H.J. (2024). Ferritin Nanoparticle Delivery of the E2 Protein of Classical Swine Fever Virus Completely Protects Pigs from Lethal Challenge. Vaccines, 12.","DOI":"10.3390\/vaccines12060629"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.virol.2020.10.007","article-title":"Immunization with a recombinant fusion of porcine reproductive and respiratory syndrome virus modified GP5 and ferritin elicits enhanced protective immunity in pigs","volume":"552","author":"Ma","year":"2021","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1186\/s12951-022-01710-4","article-title":"A modular and self-adjuvanted multivalent vaccine platform based on porcine circovirus virus-like nanoparticles","volume":"20","author":"Liu","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sookhoo, J.R.V., Schiffman, Z., Ambagala, A., Kobasa, D., Pardee, K., and Babiuk, S. (2024). Protein Expression Platforms and the Challenges of Viral Antigen Production. Vaccines, 12.","DOI":"10.3390\/vaccines12121344"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1016\/j.biotechadv.2015.10.015","article-title":"The art of CHO cell engineering: A comprehensive retrospect and future perspectives","volume":"33","author":"Fischer","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110824","DOI":"10.1016\/j.virol.2026.110824","article-title":"A bivalent subunit vaccine elicits robust immune responses and neutralizing antibodies against genogroup 1b and 2b porcine epidemic diarrhea viruses","volume":"617","author":"Sharma","year":"2026","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17749","DOI":"10.1021\/acsnano.4c03075","article-title":"A Nanoparticle Vaccine Displaying Conserved Epitopes of the Preexisting Neutralizing Antibody Confers Broad Protection against SARS-CoV-2 Variants","volume":"18","author":"Wu","year":"2024","journal-title":"ACS Nano"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41423-021-00643-6","article-title":"Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice","volume":"18","author":"Wang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.immuni.2020.11.015","article-title":"Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses","volume":"53","author":"Ma","year":"2020","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-021-03365-x","article-title":"Quadrivalent influenza nanoparticle vaccines induce broad protection","volume":"592","author":"Ellis","year":"2021","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12235","DOI":"10.1021\/acsnano.4c00809","article-title":"Combination of S1-N-Terminal and S1-C-Terminal Domain Antigens Targeting Double Receptor-Binding Domains Bolsters Protective Immunity of a Nanoparticle Vaccine against Porcine Epidemic Diarrhea Virus","volume":"18","author":"Yang","year":"2024","journal-title":"ACS Nano"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4492","DOI":"10.1021\/acsbiomaterials.5c00778","article-title":"Ferritin Complex Vaccine against Porcine Epidemic Diarrhea Virus (PEDV) Using Screened Immunogenic Sequences from Fv-Antibody Library","volume":"11","author":"Kim","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, L.J., Yin, S.H., Zhou, J.J., Zhang, L.P., Teng, Z.D., Qiao, L., Wang, Y.H., Yu, J.X., Zang, H.Y., and Ding, Y.Z. (2024). Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1386136"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13567-025-01559-z","article-title":"A bacteriophage-based virus-like particle vaccine induces cross-reactive neutralising antibodies against porcine epidemic diarrhoea viruses (PEDV)","volume":"56","author":"Gu","year":"2025","journal-title":"Vet. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110003","DOI":"10.1016\/j.vetmic.2024.110003","article-title":"Enhancing humoral and mucosal immune response of PED vaccine candidate by fusing S1 protein to nanoparticle multimerization","volume":"290","author":"Li","year":"2024","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, Y.H., Song, J.H., Deng, X.Y., Wang, J.N., Zhang, M., Liu, Y., Tang, P., Liu, H.L., Zhou, Y.J., and Tong, G.Z. (2024). Nanoparticle vaccines based on the receptor binding domain of porcine deltacoronavirus elicit robust protective immune responses in mice. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1328266"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3230453","DOI":"10.1155\/tbed\/3230453","article-title":"Design of Mucosal Vaccines Against Swine Enteric Coronaviruses: From Antigen Delivery to Immune Activation","volume":"2025","author":"Pan","year":"2025","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cao, S.N., Ma, D.X., Ji, S.W., Zhou, M., and Zhu, S.Y. (2024). Self-Assembled Ferritin Nanoparticles for Delivery of Antigens and Development of Vaccines: From Structure and Property to Applications. Molecules, 29.","DOI":"10.3390\/molecules29174221"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:11:53Z","timestamp":1785240713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biom16081090"],"URL":"https:\/\/doi.org\/10.3390\/biom16081090","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]}}}