{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:04:53Z","timestamp":1791821093979,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A03025124"],"award-info":[{"award-number":["2018R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["HV20C0085"],"award-info":[{"award-number":["HV20C0085"]}]},{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["HV20C0142"],"award-info":[{"award-number":["HV20C0142"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against Toxoplasma gondii and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the rhoptry protein 4 (ROP4) of T. gondii were generated. To evaluate the protection induced by the vaccines, mice were orally immunized with the ROP4-rVVs and subsequently challenge-infected with a lethal dose of T. gondii ME49 strain. Immunization with the rVVs induced higher levels of parasite-specific IgG and IgA antibody responses in sera compared to unimmunized control (NC). Upon challenge infection, significantly higher levels of IgG or IgA antibody responses in the brain, intestines, and vaginal samples were found in the immunized mice compared to NC. The ROP4-rVV vaccination elicited potent IgG and IgA secreting cell (ASC) responses, while substantially enhancing germinal center B cell, as well as CD4+ and CD8+ T cell responses from lymphoid organs. The production of pro-inflammatory cytokines IFN-\u03b3 and IL-6 in the brains was markedly diminished following immunization. The immunized mice also experienced reduced bodyweight loss and possessed fewer brain cysts than the control group. These results suggest that oral delivery of ROP4 displaying rVVs induced mucosal and systemic immunities that contributed to protection against lethal T. gondii challenge infection.<\/jats:p>","DOI":"10.3390\/vaccines10020152","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T22:59:57Z","timestamp":1642719597000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Orally Administrated Recombinant Vaccinia Virus Displaying ROP4 Induces Protection against Toxoplasma gondii Challenge Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Keon-Woong","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Back","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"},{"name":"Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Ji","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi-Deok","family":"Eom","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-9339","authenticated-orcid":false,"given":"Fu-Shi","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"},{"name":"Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.3389\/fmicb.2018.02587","article-title":"Drug Resistance in Toxoplasma gondii","volume":"9","author":"Montazeri","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27041","DOI":"10.3402\/jmahp.v3.27041","article-title":"Vaccination: The cornerstone of an efficient healthcare system","volume":"3","author":"Heckmann","year":"2015","journal-title":"J. Mark. Access Health Policy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1017\/S0031182003004761","article-title":"MVA ROP2 vaccinia virus recombinant as a vaccine candidate for toxoplasmosis","volume":"128","author":"Rosales","year":"2004","journal-title":"Parasitology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1017\/S0031182007002892","article-title":"A heterologous prime-boost vaccination regime using DNA and a vaccinia virus, both expressing GRA4, induced protective immunity against Toxoplasma gondii infection in mice","volume":"134","author":"Zhang","year":"2007","journal-title":"Parasitology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mendes, \u00c9.A., Fonseca, F.G., Cas\u00e9rio, B.M., Colina, J.P., Gazzinelli, R.T., and Caetano, B.C. (2013). Recombinant vaccines against T. gondii: Comparison between homologous and heterologous vaccination protocols using two viral vectors expressing SAG1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063201"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El Hajj, H., Lebrun, M., Arold, S.T., Vial, H., Labesse, G., and Dubremetz, J.F. (2007). ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030014"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1111\/j.1462-5822.2007.00909.x","article-title":"Rhoptries are major players in Toxoplasma gondii invasion and host cell interaction","volume":"9","author":"Dubremetz","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kang, H.J., Lee, S.H., Kim, M.J., Chu, K.B., Lee, D.H., Chopra, M., Choi, H.J., Park, H., Jin, H., and Quan, F.S. (2019). Influenza Virus-Like Particles Presenting both Toxoplasma gondii ROP4 and ROP13 Enhance Protection against T. gondii Infection. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11070342"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.vetpar.2018.02.043","article-title":"Assessment of the antigenic and neuroprotective activity of the subunit anti-Toxoplasma vaccine in T. gondii experimentally infected mice","volume":"254","author":"Gatkowska","year":"2018","journal-title":"Vet. Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"735191","DOI":"10.3389\/fcimb.2021.735191","article-title":"Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice","volume":"11","author":"Yoon","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0034-5288(93)90133-Z","article-title":"Potential viral vectors for the stimulation of mucosal antibody responses against enteric viral antigens in pigs","volume":"54","author":"Tuboly","year":"1993","journal-title":"Res. Vet. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0065-3527(06)68006-8","article-title":"Vaccines for viral and parasitic diseases produced with baculovirus vectors","volume":"68","year":"2006","journal-title":"Adv. Virus Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9799","DOI":"10.1128\/JVI.77.18.9799-9808.2003","article-title":"In vitro and in vivo gene delivery by recombinant baculoviruses","volume":"77","author":"Tani","year":"2003","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/bit.27987","article-title":"Insight of oral vaccines as an alternative approach to health and disease management: An innovative intuition and challenges","volume":"119","author":"Debnath","year":"2022","journal-title":"Biotechnol. Bioeng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0378-1119(95)00149-Z","article-title":"Selection of recombinant vaccinia viruses on the basis of plaque formation","volume":"158","author":"Blasco","year":"1995","journal-title":"Gene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.virol.2004.10.005","article-title":"Modified HIV envelope proteins with enhanced binding to neutralizing monoclonal antibodies","volume":"331","author":"Kang","year":"2005","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kang, H.J., Chu, K.B., Kim, M.J., Park, H., Jin, H., Lee, S.H., Moon, E.K., and Quan, F.S. (2020). Evaluation of CpG-ODN-Adjuvanted Toxoplasma Gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12100989"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3347\/kjp.2018.56.5.429","article-title":"Virus-Like Particles Expressing Toxoplasma gondii Rhoptry Protein 18 Induces Better Protection Than Rhoptry Protein 4 against T. gondii Infection","volume":"56","author":"Kang","year":"2018","journal-title":"Korean J. Parasitol."},{"key":"ref_19","doi-asserted-by":"crossref","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":"ref_20","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1016\/j.vaccine.2018.09.065","article-title":"A single dose of African horse sickness virus (AHSV) VP2 based vaccines provides complete clinical protection in a mouse model","volume":"36","author":"Aksular","year":"2018","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.0105-2896.2005.00290.x","article-title":"Mucosal immunoglobulins","volume":"206","author":"Woof","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1172\/JCI116153","article-title":"Human Toxoplasma gondii-specific secretory immunoglobulin A reduces T. gondii infection of enterocytes in vitro","volume":"90","author":"Mack","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_23","first-page":"419","article-title":"Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis","volume":"85","author":"Brown","year":"1995","journal-title":"Immunology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1017\/S1462399411002018","article-title":"Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain","volume":"13","author":"Suzuki","year":"2011","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.bbi.2014.02.020","article-title":"The pro-inflammatory cytokine interferon-gamma is an important driver of neuropathology and behavioural sequelae in experimental pneumococcal meningitis","volume":"40","author":"Too","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/icb.1990.44","article-title":"Vaccinia virus-mediated damage of murine ovaries and protection by virus-expressed interleukin-2","volume":"68","author":"Karupiah","year":"1990","journal-title":"Immunol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1743-422X-4-22","article-title":"Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses","volume":"4","author":"Hayasaka","year":"2007","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.vaccine.2005.10.044","article-title":"Protective efficacy of an oral vaccine to reduce carriage of Borrelia burgdorferi (strain N40) in mouse and tick reservoirs","volume":"24","author":"Scheckelhoff","year":"2006","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/s41467-019-08739-4","article-title":"HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge","volume":"10","author":"Jones","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:04:43Z","timestamp":1760133883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["vaccines10020152"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10020152","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,20]]}}}