{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:34:21Z","timestamp":1792809261392,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Foot-and-mouth disease virus (FMDV) infects the host by invading mucosal epithelial cells of the respiratory or digestive tract. Therefore, establishing a specific antiviral mucosal immune barrier can effectively block viral invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated local mucosal and systemic immune responses elicited by intranasal immunization of mice with foot-and-mouth disease (FMD) calcium phosphate mineralized virus-like particles (CaP-VLPs) and tested whether three commercial mucosal adjuvants enhanced the immunogenicity of the antigen. The biosafety of the vaccine was verified through gross observation and pathological analysis of the lungs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CaP-VLPs effectively induced secretion of IgA (sIgA) from multiple sites in mouse mucosa and produced anti-FMD-specific IgG in the serum. Splenic lymphocytes specifically proliferated and secreted IFN-\u03b3 following antigen stimulation, indicating the vaccine can induce a certain level of cellular immune response. Finally, the pathological examination confirmed that CaP-VLPs did not cause substantial damage to the lungs of animals after immunization <jats:italic>via<\/jats:italic> mucosal administration. Notably, the vaccine mixed with S adjuvant increased the content of sIgA and serum IgG, and the high level of IgG in serum was maintained at least 7 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, this study reveals that FMD CaP-VLPs can induce good local mucosal immune and systemic immune response through intranasal immunization, and the immune response was specifically enhanced by S adjuvant. These data support that CaP-VLPs-S as a candidate mucosal vaccine for the prevention of FMD vaccine infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1112641","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T15:47:40Z","timestamp":1675439260000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Local and systemic immune responses induced by intranasal immunization with biomineralized foot-and-mouth disease virus-like particles"],"prefix":"10.3389","volume":"14","author":[{"given":"Shuo","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjia","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyuan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huichen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanghui","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/s0169-409x(01)00166-1","article-title":"Intranasal vaccination against plague, tetanus and diphtheria","volume":"51","author":"Alpar","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1177\/0300985810372509","article-title":"The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation. Identification of the nasopharynx as the primary site of infection","volume":"47","author":"Arzt","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1016\/j.biomaterials.2005.12.008","article-title":"Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD","volume":"27","author":"Balasundaram","year":"2006","journal-title":"Biomaterials"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1164\/rccm.201011-1783OC","article-title":"Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways","volume":"183","author":"Brandtzaeg","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1021\/acsnano.8b05209","article-title":"A liposome-based adjuvant containing two delivery systems with the ability to induce mucosal immunoglobulin a following a parenteral immunization","volume":"13","author":"Christensen","year":"2019","journal-title":"ACS Nano"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13287-017-0600-8","article-title":"Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma","volume":"8","author":"de Castro","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"22748","DOI":"10.1039\/c9nr05549e","article-title":"Biomineralization improves the thermostability of foot-and-mouth disease virus-like particles and the protective immune response induced","volume":"11","author":"Du","year":"2019","journal-title":"Nanoscale"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.3390\/v14061174","article-title":"A glycolipid \u03b1-GalCer derivative, 7DW8-5 as a novel mucosal adjuvant for the Split inactivated influenza vaccine","volume":"14","author":"Feng","year":"2022","journal-title":"Viruses"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.nbt.2017.07.010","article-title":"Production of virus-like particles for vaccines","volume":"39","author":"Fuenmayor","year":"2017","journal-title":"New Biotechnol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1128\/cmr.17.2.465-493.2004","article-title":"Foot-and-mouth disease","volume":"17","author":"Grubman","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"891","DOI":"10.3390\/vaccines9080891","article-title":"Four simple biomimetic mineralization methods to improve the Thermostability and immunogenicity of virus-like particles as a vaccine against foot-and-mouth disease","volume":"9","author":"Guo","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1297-9716-44-48","article-title":"Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in Guinea pigs, swine and cattle","volume":"44","author":"Guo","year":"2013","journal-title":"Vet. Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0130821","DOI":"10.1128\/jvi.01308-21","article-title":"Structures of foot-and-mouth disease virus with bovine neutralizing antibodies reveal the determinant of intraserotype cross-neutralization","volume":"95","author":"He","year":"2021","journal-title":"J. Virol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1128\/cdli.9.5.1021-1024.2002","article-title":"Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2","volume":"9","author":"He","year":"2002","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/s0169-409x(01)00165-x","article-title":"Immunostimulating complexes (ISCOMs) for nasal vaccination","volume":"51","author":"Hu","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1016\/s0264-410x(98)00066-8","article-title":"Systemic and mucosal immune responses of mice to aluminium-adsorbed or aluminium-non-adsorbed tetanus toxoid administered intranasally with recombinant cholera toxin B subunit","volume":"16","author":"Isaka","year":"1998","journal-title":"Vaccine"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.vaccine.2021.11.030","article-title":"Development of a safe and effective novel synthetic mucosal adjuvant SF-10 derived from physiological metabolic pathways and function of human pulmonary surfactant","volume":"40","author":"Kimoto","year":"2022","journal-title":"Vaccine"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.prevetmed.2013.07.013","article-title":"The economic impacts of foot and mouth disease - what are they, how big are they and where do they occur?","volume":"112","author":"Knight-Jones","year":"2013","journal-title":"Prev. Vet. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"6221","DOI":"10.4049\/jimmunol.1202654","article-title":"Immunization with biodegradable nanoparticles efficiently induces cellular immunity and protects against influenza virus infection","volume":"190","author":"Knuschke","year":"2013","journal-title":"J. Immunol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1865-1682.2008.01027.x","article-title":"Techniques developed in China for foot-and-mouth disease diagnosis","volume":"55","author":"Lu","year":"2008","journal-title":"Transbound. Emerg. Dis."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/nri3251","article-title":"Recent progress in mucosal vaccine development: potential and limitations","volume":"12","author":"Lycke","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/1743-422x-8-419","article-title":"An overview on ELISA techniques for FMD","volume":"8","author":"Ma","year":"2011","journal-title":"Virol. J."},{"key":"ref23","first-page":"1","article-title":"NTP toxicology and carcinogenesis studies of pyridine (CAS no. 110-86-1) in F344\/N rats, Wistar rats, and B6C3F1 mice (drinking water studies)","volume":"470","year":"2000","journal-title":"Natl. Toxicol. Program Tech. Rep. Ser."},{"key":"ref24","first-page":"1","article-title":"Toxicology and carcinogenesis studies of 4-methylimidazole (Cas no. 822-36-6) in F344\/N rats and B6C3F1 mice (feed studies)","volume":"535","year":"2007","journal-title":"Natl. Toxicol. Program Tech. Rep. Ser."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.3390\/v13061137","article-title":"Changes in cell-mediated immunity (ifn-\u03b3 and granzyme b) following influenza vaccination","volume":"13","author":"Otani","year":"2021","journal-title":"Viruses"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.tvjl.2008.08.023","article-title":"Early events in the pathogenesis of foot-and-mouth disease in cattle after controlled aerosol exposure","volume":"183","author":"Pacheco","year":"2010","journal-title":"Vet. J."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1586\/14760584.8.3.347","article-title":"Vaccination against foot-and-mouth disease virus: strategies and effectiveness","volume":"8","author":"Parida","year":"2009","journal-title":"Expert Rev. Vaccines"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.antiviral.2007.05.005","article-title":"Humoral and cellular immune responses to airway immunization of mice with human papillomavirus type 16 virus-like particles and mucosal adjuvants","volume":"76","author":"Revaz","year":"2007","journal-title":"Antivir. Res."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2446","DOI":"10.1111\/all.15311","article-title":"Intranasal administration of a VLP-based vaccine induces neutralizing antibodies against SARS-CoV-2 and variants of concern","volume":"77","author":"Rothen","year":"2022","journal-title":"Allergy"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.tvjl.2007.03.009","article-title":"Foot-and-mouth disease: a review of intranasal infection of cattle, sheep and pigs","volume":"177","author":"Sellers","year":"2008","journal-title":"Vet. J."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/s41467-018-08265-9","article-title":"Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins","volume":"10","author":"Serradell","year":"2019","journal-title":"Nat. Commun."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3389\/fvets.2016.00041","article-title":"The pathogenesis of foot-and-mouth disease in pigs","volume":"3","author":"Stenfeldt","year":"2016","journal-title":"Front. Vet. Sci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e0143666","DOI":"10.1371\/journal.pone.0143666","article-title":"Pathogenesis of primary foot-and-mouth disease virus infection in the nasopharynx of vaccinated and non-vaccinated cattle","volume":"10","author":"Stenfeldt","year":"2015","journal-title":"PLoS One"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e00493","DOI":"10.1128\/mSphere.00493-18","article-title":"Contact challenge of cattle with foot-and-mouth disease virus validates the role of the nasopharyngeal epithelium as the site of primary and persistent infection","volume":"3","author":"Stenfeldt","year":"2018","journal-title":"mSphere"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.rvsc.2014.01.009","article-title":"Infection dynamics of foot-and-mouth disease virus in pigs using two novel simulated-natural inoculation methods","volume":"96","author":"Stenfeldt","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1002\/adma.201503740","article-title":"Vaccine engineering with dual-functional mineral shell: a promising strategy to overcome preexisting immunity","volume":"28","author":"Wang","year":"2016","journal-title":"Adv. Mater."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"5894","DOI":"10.1073\/pnas.83.16.5894","article-title":"Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell-and T-cell-stimulating activities","volume":"83","author":"Yokota","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. 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