{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T20:56:00Z","timestamp":1769028960858,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFF1305400"],"award-info":[{"award-number":["2023YFF1305400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies\u2019 response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.<\/jats:p>","DOI":"10.3390\/v16040549","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:44:52Z","timestamp":1711892692000},"page":"549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Bacterium-like Particle Vaccine Displaying Envelope Proteins of Canine Distemper Virus Can Induce Immune Responses in Mice and Dogs"],"prefix":"10.3390","volume":"16","author":[{"given":"Lina","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130000, China"},{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Li","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"},{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"},{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feihu","family":"Yan","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiecheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongzheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Feng","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"},{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianzhu","family":"Xia","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"},{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0969-2126(97)00233-5","article-title":"Rossmann, Structure of bacteriophage T4 fibritin: A segmented coiled coil and the role of the C-terminal domain","volume":"5","author":"Tao","year":"1997","journal-title":"Structure"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-1135(89)90043-6","article-title":"Natural infection with canine distemper virus in a Japanese monkey (Macaca fuscata)","volume":"20","author":"Yoshikawa","year":"1989","journal-title":"Vet. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/104063879400600301","article-title":"Canine distemper epizootic in lions, tigers, and leopards in North America","volume":"6","author":"Appel","year":"1994","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1638\/1042-7260-48.4.1250","article-title":"Serologic response to canine distemper vaccination in captive linnaeus\u2019s two-toed sloths (choloepus didactylus) after a fatal canine distemper virus outbreak","volume":"48","author":"Sheldon","year":"2017","journal-title":"J. Zoo Wildl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/tbed.13456","article-title":"Immunohistochemical evidence of canine morbillivirus (canine distemper) infection in coatis (Nasua nasua) from Southern Brazil","volume":"67","author":"Michelazzo","year":"2020","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.vetmic.2011.05.008","article-title":"Urban domestic dog populations as a source of canine distemper virus for wild carnivores in the Coquimbo region of Chile","volume":"152","author":"Chalmers","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1292\/jvms.15-0237","article-title":"Canine distemper virus infection among wildlife before and after the epidemic","volume":"77","author":"Suzuki","year":"2015","journal-title":"J. Vet. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"682","DOI":"10.7589\/2018-07-175","article-title":"Effect of Canine Parvovirus and Canine Distemper Virus on the Mexican Wolf (Canis lupus baileyi) Population in the USA","volume":"55","author":"Clement","year":"2019","journal-title":"J. Wildl. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"482","DOI":"10.7589\/2019-08-195","article-title":"An Eight-Year Survey for Canine Distemper Virus Indicates Lack of Exposure in the Endangered Darwin\u2019s Fox (Lycalopex fulvipes)","volume":"56","author":"Cabello","year":"2020","journal-title":"J. Wildl. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3201\/eid2105.141920","article-title":"Canine distemper in endangered Ethiopian wolves","volume":"21","author":"Gordon","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.tvjl.2014.01.028","article-title":"Emergence of canine distemper virus strains with two amino acid substitutions in the haemagglutinin protein, detected from vaccinated carnivores in North-Eastern China in 2012\u20132013","volume":"200","author":"Zhao","year":"2014","journal-title":"Vet. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6418","DOI":"10.1128\/JVI.75.14.6418-6427.2001","article-title":"The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity","volume":"75","author":"Zimmer","year":"2001","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12985-019-1136-6","article-title":"Tropism and molecular pathogenesis of canine distemper virus","volume":"16","author":"Canal","year":"2019","journal-title":"Virol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1292\/jvms.65.109","article-title":"Cytotoxic T-lymphocyte activity specific for hemagglutinin (H) protein of canine distemper virus in dogs","volume":"65","author":"Hirama","year":"2003","journal-title":"J. Vet. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1128\/jvi.58.2.536-541.1986","article-title":"Protection against canine distemper virus in dogs after immunization with isolated fusion protein","volume":"58","author":"Norrby","year":"1986","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1128\/AEM.72.1.880-889.2006","article-title":"Novel surface display system for proteins on non-genetically modified gram-positive bacteria","volume":"72","author":"Bosma","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1016\/j.vaccine.2006.09.026","article-title":"Development of lactococcal GEM-based pneumococcal vaccines","volume":"25","author":"Audouy","year":"2007","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1016\/j.vaccine.2006.02.040","article-title":"Immunogenicity of a malaria parasite antigen displayed by Lactococcus lactis in oral immunisations","volume":"24","author":"Ramasamy","year":"2006","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1475-2875-11-50","article-title":"Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice","volume":"11","author":"Leenhouts","year":"2012","journal-title":"Malar. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, E., Chi, H., Huang, P., Yan, F., Zhang, Y., Liu, C., Wang, Z., Li, G., Zhang, S., and Mo, R. (2019). A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice. Viruses, 11.","DOI":"10.3390\/v11090799"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xu, S., Jiao, C., Jin, H., Li, W., Li, E., Cao, Z., Shi, Z., Yan, F., Zhang, S., and He, H. (2019). A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice. Viruses, 11.","DOI":"10.3390\/v11121149"},{"key":"ref_22","first-page":"282","article-title":"Bacterium-like particles for efficient immune stimulation of existing vaccines and new subunit vaccines in mucosal applications","volume":"4","author":"Haijema","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/mi.2009.131","article-title":"Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection","volume":"3","author":"Ramirez","year":"2010","journal-title":"Mucosal Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1016\/j.vaccine.2006.03.054","article-title":"Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization","volume":"24","author":"Audouy","year":"2006","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ymeth.2005.09.015","article-title":"Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria","volume":"38","author":"Kanninga","year":"2006","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27518","DOI":"10.1038\/srep27518","article-title":"Fatal canine distemper virus infection of giant pandas in China","volume":"6","author":"Feng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wilkes, R.P. (2022). Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination. Pathogens, 12.","DOI":"10.3390\/pathogens12010057"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1074\/jbc.REV119.009961","article-title":"Receptor-mediated cell entry of paramyxoviruses: Mechanisms, and consequences for tropism and pathogenesis","volume":"295","author":"Navaratnarajah","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00413-13","DOI":"10.1128\/mBio.00413-13","article-title":"Envelope protein dynamics in paramyxovirus entry","volume":"4","author":"Plattet","year":"2013","journal-title":"mBio"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1046\/j.1432-1033.2002.02734.x","article-title":"Domain organization, folding and stability of bacteriophage T4 fibritin, a segmented coiled-coil protein","volume":"269","author":"Boudko","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_31","first-page":"817","article-title":"The carboxy-terminal domain initiates trimerization of bacteriophage T4 fibritin","volume":"64","author":"Letarov","year":"1999","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.jmb.2004.02.020","article-title":"Very fast folding and association of a trimerization domain from bacteriophage T4 fibritin","volume":"337","author":"Kapinos","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.addr.2012.09.039","article-title":"Fusion protein linkers: Property, design and functionality","volume":"65","author":"Chen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e02077-16","DOI":"10.1128\/JVI.02077-16","article-title":"Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens","volume":"91","author":"Hudacek","year":"2017","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1128\/JVI.74.14.6358-6367.2000","article-title":"Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines","volume":"74","author":"Welter","year":"2000","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.4049\/jimmunol.1200092","article-title":"Uptake of particulate antigens in a nonmammalian lung: Phenotypic and functional characterization of avian respiratory phagocytes using bacterial or viral antigens","volume":"188","author":"Jansen","year":"2012","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1080\/03079457.2015.1026797","article-title":"Distribution patterns of mucosally applied particles and characterization of the antigen presenting cells","volume":"44","author":"Degen","year":"2015","journal-title":"Avian Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.4049\/jimmunol.178.11.6715","article-title":"Cutting edge: TLR2 directly triggers Th1 effector functions","volume":"178","author":"Imanishi","year":"2007","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.7589\/0090-3558-40.2.343","article-title":"Immunogenicity of an inactivated oil-emulsion canine distemper vaccine in African wild dogs","volume":"40","author":"Cirone","year":"2004","journal-title":"J. Wildl. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1016\/S0264-410X(00)00119-5","article-title":"DNA vaccine encoding nucleocapsid and surface proteins of wild type canine distemper virus protects its natural host against distemper","volume":"18","author":"Cherpillod","year":"2000","journal-title":"Vaccine"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/549\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:48Z","timestamp":1760106108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/4\/549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,31]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["v16040549"],"URL":"https:\/\/doi.org\/10.3390\/v16040549","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,31]]}}}