{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:03:49Z","timestamp":1777579429726,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"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":["NRF-2018-R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018-R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background:\u00a0Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this study, we generated virus-like particles (VLPs) and recombinant vaccinia virus (rVV) containing MIC8 or AMA1 proteins. Vaccine efficacy was evaluated in mice (BALB\/c) upon challenge infection with T. gondii ME49. Results: Intramuscular immunization with heterologous vaccines (rVV + VLPs; rVV for prime and VLPs for boost) elicited T. gondii-specific IgG antibody responses in mice. Four weeks after the boost, all mice were orally challenged with T. gondii ME49, and protective immunity was assessed. The responses of antibody-secreting cells for IgG2a and IgG2b and those of memory B cells and CD4+ and CD8+ T cells were higher in the rVV + VLP group than in the VLP + VLP group. The rVV + VLP group exhibited a significant reduction in cyst count in the brain. Conclusions: These findings indicate that heterologous vaccination with vaccinia viruses and VLPs improves vaccine efficacy.<\/jats:p>","DOI":"10.3390\/vaccines13080862","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:39:07Z","timestamp":1755247147000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of Heterologous Vaccination Using Virus-Like Particles and Vaccinia Virus Containing MIC8 and AMA1 Proteins of Toxoplasma gondii"],"prefix":"10.3390","volume":"13","author":[{"given":"Hae-Ji","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Microbiology, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-9339","authenticated-orcid":false,"given":"Fu-Shi","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Medical Zoology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-020-04445-z","article-title":"The life-cycle of Toxoplasma gondii reviewed using animations","volume":"13","author":"Attias","year":"2020","journal-title":"Parasites Vectors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e01155-15","DOI":"10.1128\/mBio.01155-15","article-title":"Novel approaches reveal that Toxoplasma gondii bradyzoites within tissue cysts are dynamic and replicating entities in vivo","volume":"6","author":"Watts","year":"2015","journal-title":"MBio"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110872","DOI":"10.1016\/j.intimp.2023.110872","article-title":"Immune system roles in pathogenesis, prognosis, control, and treatment of Toxoplasma gondii infection","volume":"124","author":"Jafari","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0171-2985(99)80064-3","article-title":"Cell-mediated immunity to Toxoplasma gondii: Initiation, regulation and effector function","volume":"201","author":"Yap","year":"1999","journal-title":"Immunobiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nrmicro2858","article-title":"Modulation of innate immunity by Toxoplasma gondii virulence effectors","volume":"10","author":"Hunter","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/clinids\/7.4.449","article-title":"How does Toxoplasma gondii enter host cells?","volume":"7","author":"Werk","year":"1985","journal-title":"Rev. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1242\/jcs.022350","article-title":"Microneme protein 8\u2013a new essential invasion factor in Toxoplasma gondii","volume":"121","author":"Kessler","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1046\/j.1462-5822.1999.00023.x","article-title":"Secretion of micronemal proteins is associated with Toxoplasma invasion of host cells","volume":"1","author":"Carruthers","year":"1999","journal-title":"Cell. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1016\/j.vaccine.2018.08.016","article-title":"Virus-like particle vaccines expressing Toxoplasma gondii rhoptry protein 18 and microneme protein 8 provide enhanced protection","volume":"36","author":"Lee","year":"2018","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104090","DOI":"10.1016\/j.micpath.2020.104090","article-title":"Virus-like particle vaccine displaying Toxoplasma gondii apical membrane antigen 1 induces protection against T. gondii ME49 infection in mice","volume":"142","author":"Kim","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"994","DOI":"10.15212\/ZOONOSES-2024-0044","article-title":"Strategies for the Modification of Vaccinia Virus towards a Better Vaccine Vector","volume":"5","author":"Sun","year":"2025","journal-title":"Zoonoses"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1128\/JVI.76.7.3329-3337.2002","article-title":"Recombinant vaccinia virus-induced T-cell immunity: Quantitation of the response to the virus vector and the foreign epitope","volume":"76","author":"Harrington","year":"2002","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.4049\/jimmunol.171.10.4969","article-title":"Cutting edge: Long-term B cell memory in humans after smallpox vaccination","volume":"171","author":"Crotty","year":"2003","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1016\/j.vaccine.2017.09.028","article-title":"Safety and immunogenicity of heterologous prime-boost immunization with viral-vectored malaria vaccines adjuvanted with Matrix-M\u2122","volume":"35","author":"Venkatraman","year":"2017","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bhatnagar, N., Kim, K.-H., Subbiah, J., Muhammad-Worsham, S., Park, B.R., Liu, R., Grovenstein, P., Wang, B.-Z., and Kang, S.-M. (2023). Heterologous Prime-Boost Vaccination with Inactivated Influenza Viruses Induces More Effective Cross-Protection than Homologous Repeat Vaccination. Vaccines, 11.","DOI":"10.3390\/vaccines11071209"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1080\/22221751.2021.1957401","article-title":"Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine","volume":"10","author":"Zhang","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ho, T.-C., Chen, Y.-M.A., Chan, H.-P., Chang, C.-C., Chuang, K.-P., Lee, C.-H., Yuan, C.-H., Tyan, Y.-C., and Yang, M.-H. (2021). The effects of heterologous immunization with prime-boost COVID-19 vaccination against SARS-CoV-2. Vaccines, 9.","DOI":"10.3390\/vaccines9101163"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","unstructured":"Yoon, K.-W., Chu, K.-B., Kang, H.-J., Kim, M.-J., Eom, G.-D., and Quan, F.-S. (2022). Orally administrated recombinant vaccinia virus displaying ROP4 induces protection against Toxoplasma gondii challenge infection. Vaccines, 10.","DOI":"10.3390\/vaccines10020152"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3347\/PHD.24017","article-title":"Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1","volume":"62","author":"Kim","year":"2024","journal-title":"Parasites Hosts Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hanson, C.H., Henry, B., Andhare, P., Lin, F.J., Pak, H., Turner, J.S., Adams, L.J., Liu, T., Fremont, D.H., and Ellebedy, A.H. (2023). CD62L expression marks a functionally distinct subset of memory B cells. Cell Rep., 42.","DOI":"10.1016\/j.celrep.2023.113542"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-020-01840-2","article-title":"Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis","volume":"17","author":"Zabalza","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1134\/S0026893319030154","article-title":"Virus-like particles as an instrument of vaccine production","volume":"53","author":"Syomin","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.smim.2017.08.014","article-title":"Major findings and recent advances in virus\u2013like particle (VLP)-based vaccines","volume":"34","author":"Mohsen","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jconrel.2016.02.014","article-title":"Mucosal vaccine delivery: Current state and a pediatric perspective","volume":"240","author":"Shakya","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0167-5699(92)90083-J","article-title":"Induction of TH1 and TH2 responses: A key role for the \u2018natural\u2019immune response?","volume":"13","author":"Romagnani","year":"1992","journal-title":"Immunol. Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1016\/j.vaccine.2011.01.089","article-title":"Induction of protective Th1 immune responses in mice by vaccination with recombinant Toxoplasma gondii nucleoside triphosphate hydrolase-II","volume":"29","author":"Tan","year":"2011","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/CMR.11.4.569","article-title":"Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection","volume":"11","author":"Denkers","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.4049\/jimmunol.182.2.1069","article-title":"Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication","volume":"182","author":"Gigley","year":"2009","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1126\/science.1065543","article-title":"Distinct effects of T-bet in TH1 lineage commitment and IFN-\u03b3 production in CD4 and CD8 T cells","volume":"295","author":"Szabo","year":"2002","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Jiang, N., Zhang, T., Wang, D., Feng, Y., Sang, X., Yang, N., and Chen, Q. (2018). Toxoplasma gondii genotype determines Tim-3 expression levels in splenic and circulatory T cells in mice. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02967"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nri3128","article-title":"Molecular programming of B cell memory","volume":"12","author":"Okitsu","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","first-page":"925135","article-title":"CD4+ T cells: Differentiation and functions","volume":"2012","author":"Luckheeram","year":"2012","journal-title":"J. Immunol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/intimm\/dxad017","article-title":"Memory B cell differentiation from germinal centers","volume":"35","author":"Inoue","year":"2023","journal-title":"Int. Immunol."},{"key":"ref_35","first-page":"499","article-title":"European journals of microbiology","volume":"13","author":"Ronda","year":"1997","journal-title":"Microbiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s13071-022-05596-x","article-title":"Chronic Toxoplasma gondii infection contributes to perineuronal nets impairment in the primary somatosensory cortex","volume":"15","author":"Meurer","year":"2022","journal-title":"Parasites Vectors"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1080\/17435889.2024.2403333","article-title":"Heterologous immunization targeting the CST1 antigen confers better protection than ROP18 in mice","volume":"19","author":"Eom","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Eom, G.-D., Chu, K.-B., Kang, H.-J., Kim, M.-J., Yoon, K.-W., Mao, J., Lee, S.-H., Ahmed, M.A., Moon, E.-K., and Quan, F.-S. (2023). Protective mucosal and systemic immunity induced by virus-like particles expressing Toxoplasma gondii cyst wall protein. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0283928"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/8\/862\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:28:05Z","timestamp":1760034485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/8\/862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["vaccines13080862"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13080862","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]}}}