{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:52:20Z","timestamp":1790607140888,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific Research at Qassim University","award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}]},{"award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}],"id":[{"id":"https:\/\/ror.org\/01wsfe280","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite\u2019s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR\/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals\u2014prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis.<\/jats:p>","DOI":"10.3390\/vetsci13050437","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Advances and Translational Challenges in Toxoplasma gondii Vaccine Development: From Antigen Discovery to mRNA and One Health Strategies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0268-1167","authenticated-orcid":false,"given":"Abdul","family":"Qadeer","sequence":"first","affiliation":[{"name":"School of Medical Sciences, Shandong Xiehe University, Jinan 250109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-9590","authenticated-orcid":false,"given":"Mohamed","family":"Tharwat","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2996","authenticated-orcid":false,"given":"Muhammad Zahoor","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Juhasz","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Semmelweis University, H-1089 Budapest, Hungary"},{"name":"Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-4301","authenticated-orcid":false,"given":"Fahad A.","family":"Alshanbari","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Qadeer, A., An, H.Y., Wakid, M.H., Hussain, S., Asiri, M., Alzahrani, F.M., Alzahrani, K.J., Alsharif, K.F., Chen, C.C., and Ahmad, I. (2025). Toxoplasmosis awareness among women: A cross-sectional study on knowledge, attitudes, perceptions, and risk factors. BMC Public Health, 25.","DOI":"10.1186\/s12889-025-25286-4"},{"key":"ref_2","first-page":"745","article-title":"Serological identification of Toxoplasma gondii in Goats and their Female Possessors in Kurram District of Khyber Pakhtunkhwa","volume":"57","author":"Shaukat","year":"2025","journal-title":"Pak. Pak. J. Zool."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2024.2396577","article-title":"The global seroprevalence of Toxoplasma gondii infection in workers occupationally exposed to animals (1972\u20132023): A systematic review and meta-analysis","volume":"44","author":"Mohammed","year":"2024","journal-title":"Vet. Q."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e31558","DOI":"10.1016\/j.heliyon.2024.e31558","article-title":"Effective factors in the pathogenesis of Toxoplasma gondii","volume":"10","author":"Nayeri","year":"2024","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00436-024-08189-y","article-title":"Observational longitudinal study on Toxoplasma gondii infection in fattening beef cattle: Serology and associated haematological findings","volume":"123","author":"Dini","year":"2024","journal-title":"Parasitol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Farhab, M., Aziz, M.W., Shaukat, A., Cao, M.-X., Hou, Z., Huang, S.-Y., Li, L., and Yuan, Y.-G. (2025). Review of Toxoplasmosis: What We Still Need to Do. Vet. Sci., 12.","DOI":"10.3390\/vetsci12080772"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Latifi, A., and Flegr, J. (2025). Beyond Latency: Chronic Toxoplasma Infection and Its Unveiled Behavioral and Clinical Manifestations\u2014A 30-Year Research Perspective. Biomedicines, 13.","DOI":"10.3390\/biomedicines13071731"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.3390\/microorganisms9122531","article-title":"Toxoplasmosis: Current and Emerging Parasite Druggable Targets","volume":"9","author":"Hajj","year":"2021","journal-title":"Microorganisms"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.pt.2019.01.005","article-title":"Advances in the Development of Anti-Toxoplasma gondii Vaccines: Challenges, Opportunities, and Perspectives","volume":"35","author":"Wang","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S1286-4579(03)00048-0","article-title":"Development of a vaccine for toxoplasmosis: Current status","volume":"5","author":"Bhopale","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chu, K.B., and Quan, F.S. (2021). Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development. Vaccines, 9.","DOI":"10.3390\/vaccines9050413"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41541-022-00563-0","article-title":"Toxoplasmosis vaccines: What we have and where to go?","volume":"7","author":"Zhang","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"M\u00e9v\u00e9lec, M.N., Lakhrif, Z., and Dimier-Poisson, I. (2020). Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.607198"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1017\/S003118200000144X","article-title":"A commercial vaccine for ovine toxoplasmosis","volume":"110","author":"Buxton","year":"1995","journal-title":"Parasitology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11845-022-02998-9","article-title":"Toxoplasma gondii vaccine candidates: A concise review","volume":"192","author":"Mamaghani","year":"2023","journal-title":"Ir. J. Med. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101414","DOI":"10.1016\/j.cimid.2020.101414","article-title":"Toxoplasma gondii surface antigen 1 (SAG1) as a potential candidate to develop vaccine against toxoplasmosis: A systematic review","volume":"69","author":"Pagheh","year":"2020","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105696","DOI":"10.1016\/j.mimet.2019.105696","article-title":"A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization","volume":"165","author":"Rezaei","year":"2019","journal-title":"J. Microbiol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.3390\/ani12091098","article-title":"Mining the proteome of toxoplasma parasites seeking vaccine and diagnostic candidates","volume":"12","author":"Rashidi","year":"2022","journal-title":"Animals"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1645\/20-157","article-title":"Review of DNA vaccine approaches against the parasite Toxoplasma gondii","volume":"107","author":"Warner","year":"2021","journal-title":"J. Parasitol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.exppara.2017.06.002","article-title":"Evaluation of protective immunity induced by DNA vaccination with genes encoding Toxoplasma gondii GRA17 and GRA23 against acute toxoplasmosis in mice","volume":"179","author":"Zhu","year":"2017","journal-title":"Exp. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mukhopadhyay, D., Arranz-Sol\u00eds, D., and Saeij, J.P.J. (2020). Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11. PLoS Pathog., 16.","DOI":"10.1101\/2020.02.14.950360"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cimid.2018.09.005","article-title":"Vaccination against Toxoplasma gondii using rhoptry antigens: A systematic review","volume":"59","author":"Faridnia","year":"2018","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10096-018-03442-6","article-title":"A systematic review on efficiency of microneme proteins to induce protective immunity against Toxoplasma gondii","volume":"38","author":"Dodangeh","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, N.Z., Gao, Q., Wang, M., Elsheikha, H.M., Wang, B., Wang, J.L., Zhang, F.K., Hu, L.Y., and Zhu, X.Q. (2018). Immunization With a DNA Vaccine Cocktail Encoding TgPF, TgROP16, TgROP18, TgMIC6, and TgCDPK3 Genes Protects Mice Against Chronic Toxoplasmosis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01505"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111655","DOI":"10.1016\/j.molbiopara.2024.111655","article-title":"Designing a multi-epitope subunit vaccine against Toxoplasma gondii through reverse vaccinology approach","volume":"260","author":"Ahmed","year":"2024","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106462","DOI":"10.1016\/j.applanim.2024.106462","article-title":"Exploring the relationship between Toxoplasma gondii seropositivity and anxiety disorders in companion dogs (Canis lupus familiaris)","volume":"282","author":"Dini","year":"2025","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107501","DOI":"10.1016\/j.actatropica.2024.107501","article-title":"Protective humoral immunity induced by virus-like particles expressing Toxoplasma gondii CST1 or MIC8","volume":"261","author":"Mao","year":"2025","journal-title":"Acta Trop."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-1-4939-6472-7_6","article-title":"Development of CRISPR\/Cas9 for Efficient Genome Editing in Toxoplasma gondii","volume":"1498","author":"Shen","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, J.L., Elsheikha, H.M., Zhu, W.N., Chen, K., Li, T.T., Yue, D.M., Zhang, X.X., Huang, S.Y., and Zhu, X.Q. (2017). Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial Protection and Survival in Challenged Mice. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00730"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41541-024-00996-9","article-title":"Toxoplasma WH3 \u0394rop18 acts as a live attenuated vaccine against acute and chronic toxoplasmosis","volume":"9","author":"Wang","year":"2024","journal-title":"NPJ Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41541-022-00518-5","article-title":"Live-attenuated ME49\u0394cdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis","volume":"7","author":"Wu","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40249-023-01109-9","article-title":"A live attenuated RH\u0394ompdc\u0394uprt mutant of Toxoplasma gondii induces strong protective immunity against toxoplasmosis in mice and cats","volume":"12","author":"Shen","year":"2023","journal-title":"Infect. Dis. Poverty"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13568-025-01889-3","article-title":"Comparative evaluation of live attenuated and killed tachyzoites as vaccine candidates for toxoplasmosis","volume":"15","author":"Nemr","year":"2025","journal-title":"AMB. Express"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70143","DOI":"10.1111\/1751-7915.70143","article-title":"Toxoplasma gondii C2 Domain Protein Deletion Mutant as a Promising Vaccine Against Toxoplasmosis in Mice","volume":"18","author":"Luo","year":"2025","journal-title":"Microb. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"126632","DOI":"10.1016\/j.vaccine.2024.126632","article-title":"Evaluation of the toxoplasma Urm1 gene deletion mutant (Pru\u0394Urm1) as a promising vaccine candidate against toxoplasmosis in mice","volume":"45","author":"Bian","year":"2025","journal-title":"Vaccine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1038\/s41598-018-37671-8","article-title":"An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats","volume":"9","author":"Ramakrishnan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chen, M., Yang, P., Xin, Z., Chen, J., Zou, W., Zhou, L., Yang, L., Peng, J., and Peng, H. (2023). Toxoplasma gondii gra5 deletion mutant protects hosts against Toxoplasma gondii infection and breast tumors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1173379"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2400952","DOI":"10.1002\/advs.202400952","article-title":"The Toxoplasma Effector GRA4 Hijacks Host TBK1 to Oppositely Regulate Anti-T. gondii Immunity and Tumor Immunotherapy","volume":"11","author":"Hu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107567","DOI":"10.1016\/j.micpath.2025.107567","article-title":"Designing a multi-epitope vaccine using Toxoplasma ROP5, ROP7, and SAG1 epitopes and immunogenicity evaluation against acute and chronic toxoplasmosis in BABL\/c mice","volume":"204","author":"Moghadamizad","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107321","DOI":"10.1016\/j.micpath.2025.107321","article-title":"Immunogenicity of an in-silico designed multi-epitope DNA vaccine encoding ROP21 and ROP29 of Toxoplasma gondii against both acute and chronic toxoplasmosis in BALB\/c mice","volume":"200","author":"Ghaffarifar","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Fang, Y., Zhou, P., Qi, W., Yu, Y., Wang, X., Jiang, Y., Zhang, L., Yu, Y., Wang, J., and Yu, Z. (2025). Research on inner membrane complex protein 1: A novel nanovaccines against Toxoplasma gondii. BMC Vet. Res., 21.","DOI":"10.1186\/s12917-025-04961-z"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Xu, B., Zhang, X., Wang, Y., and Chen, J. (2025). IL-24 Is a Promising Molecular Adjuvant for Enhancing Protective Immunity Induced by DNA Vaccination Against Toxoplasma gondii. Microorganisms, 13.","DOI":"10.3390\/microorganisms13071661"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s00436-024-08435-3","article-title":"Vaccination with a DNA vaccine cocktail encoding TgROP2, TgROP5, TgROP9, TgROP16, TgROP17, and TgROP18 confers limited protection against Toxoplasma gondii in BALB\/c mice","volume":"123","author":"Du","year":"2024","journal-title":"Parasitol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tan, Y., Mu, J., and Chen, J. (2024). IL-36 Gamma: A Novel Adjuvant Cytokine Enhancing Protective Immunity Induced by DNA Immunization with TGIST and TGNSM Against Toxoplasma gondii Infection in Mice. Microorganisms, 12.","DOI":"10.3390\/microorganisms12112258"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shi, Y., Li, J., Yang, W., and Chen, J. (2023). Protective immunity induced by DNA vaccine containing TgGRA35, TgGRA42, and TgGRA43 against Toxoplasma gondii infection in Kunming mice. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1236130"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108409","DOI":"10.1016\/j.exppara.2022.108409","article-title":"Immunological evaluation of a novel multi-antigenic DNA vaccine encoding SAG1, SAG3, MIC4, GRA5, GRA7, AMA1and BAG1 against Toxoplasma gondii in BALB\/c mice","volume":"244","author":"Alijani","year":"2023","journal-title":"Exp. Parasitol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"359","DOI":"10.7774\/cevr.2024.13.4.359","article-title":"Completing the pieces of a puzzle: In-depth probing of Toxoplasma gondii rhoptry protein 4 as a promising target for vaccination using an in-silico approach","volume":"13","author":"Foroutan","year":"2024","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12976","DOI":"10.1038\/s41598-023-40147-z","article-title":"Evaluation of long-term immunity and protection against T. gondii after immunization with multivalent recombinant chimeric T. gondii proteins","volume":"13","author":"Chyb","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"32979","DOI":"10.1038\/s41598-025-14988-9","article-title":"Recombinant ROP6 protein expressed in Saccharomyces cerevisiae INVSc1 cells induced strong immune response and provided significant protection against toxoplasmosis","volume":"15","author":"Karakavuk","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"107780","DOI":"10.1016\/j.actatropica.2025.107780","article-title":"Recombinant TgDDX3X DEAD-box protein confers partial protection in murine models of acute and chronic toxoplasmosis","volume":"270","author":"Wang","year":"2025","journal-title":"Acta Trop."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Li, X., Yuan, W., He, T., Guo, R., Du, X., He, Y., Li, X., El-Ashram, S., Al-Olayan, E.M., and Yang, N. (2023). Boosting Mouse Defense against Lethal Toxoplasma gondii Infection with Full-Length and Soluble SAG1 Recombinant Protein. Vaccines, 11.","DOI":"10.3390\/vaccines11111678"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106883","DOI":"10.1016\/j.actatropica.2023.106883","article-title":"Recombinant Toxoplasma gondii Calreticulin protein provides partial protection against acute and chronic toxoplasmosis","volume":"241","author":"Zhang","year":"2023","journal-title":"Acta Trop."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107442","DOI":"10.1016\/j.actatropica.2024.107442","article-title":"Evaluation of protective efficacy of recombinant Toxoplasma gondii DDX39 protein vaccine against acute and chronic T. gondii infection in mice","volume":"260","author":"Wang","year":"2024","journal-title":"Acta Trop."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.vaccine.2024.01.050","article-title":"Protective effect against toxoplasmosis in BALB\/C mice vaccinated with recombinant Toxoplasma gondii CDPK3, GRA35, and ROP46 protein cocktail vaccine","volume":"42","author":"Li","year":"2024","journal-title":"Vaccine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/j.vaccine.2024.02.062","article-title":"Protective efficacy of recombinant Toxoplasma gondii dense granule protein 15 against toxoplasmosis in C57BL\/6 mice","volume":"42","author":"Hasan","year":"2024","journal-title":"Vaccine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.coi.2020.01.008","article-title":"Recent advances in mRNA vaccine technology","volume":"65","author":"Pardi","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Luo, F., Zheng, L., Hu, Y., Liu, S., Wang, Y., Xiong, Z., Hu, X., and Tan, F. (2017). Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP). Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00605"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s40249-025-01332-6","article-title":"A novel combined quadrivalent self-amplifying mRNA-LNP vaccine provokes protective immunity against acute and chronic toxoplasmosis in mice","volume":"14","author":"Wu","year":"2025","journal-title":"Infect. Dis. Poverty"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e0286623","DOI":"10.1128\/spectrum.02866-23","article-title":"A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB\/c mice with acute toxoplasmosis","volume":"12","author":"Zhang","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Li, D., Zhang, Y., Li, S., and Zheng, B. (2023). A novel Toxoplasma gondii TGGT1_316290 mRNA-LNP vaccine elicits protective immune response against toxoplasmosis in mice. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1145114"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"149073","DOI":"10.1016\/j.gene.2024.149073","article-title":"An optimized ROP6 mRNA construct successfully expressed immunogenic Toxoplasma gondii ROP6 protein in cell culture","volume":"935","author":"Karakavuk","year":"2025","journal-title":"Gene"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105312","DOI":"10.1016\/j.micpath.2021.105312","article-title":"Co-delivery of PLGA nanoparticles loaded with rSAG1 antigen and TLR ligands: An efficient vaccine against chronic toxoplasmosis","volume":"162","author":"Allahyari","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rattanapitoon, N.K., Arunsan, P., La, N., Sandoval, K.L., and Rattanapitoon, S.K. (2025). Commentary: PLGA nanoparticles as an efficient carrier in Toxoplasma GAP45: A more effective vaccine against acute toxoplasmosis than traditional ones. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1663012"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhou, P., Yu, Y., Qi, W., Wang, X., Yu, Y., Wang, J., Zhang, L., Yu, Z., and Liu, T. (2025). PLGA nanoparticles as an efficient carrier in Toxoplasma GAP45: A more effective vaccine against acute toxoplasmosis than traditional ones. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1600399"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Qi, W., Yu, Y., Yang, C., Wang, X., Jiang, Y., Zhang, L., and Yu, Z. (2024). Nanospheres as the delivery vehicle: Novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1475280"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"106092","DOI":"10.1016\/j.micpath.2023.106092","article-title":"Immunological evaluation of a recombinant vaccine delivered with an analogous hyaluronic acid chitosan nanoparticle-hydrogel against Toxoplasma gondii in mice","volume":"179","author":"Li","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sun, H.C., Deng, P.M., Fu, Y., Deng, J.H., Xie, R.H., Huang, J., Qi, M., and Shi, T.Y. (2023). Protective efficacy of Toxoplasma gondii GRA12 or GRA7 recombinant proteins encapsulated in PLGA nanoparticles against acute Toxoplasma gondii infection in mice. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1209755"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"106215","DOI":"10.1016\/j.actatropica.2021.106215","article-title":"Effect of alginate nanoparticles on the immunogenicity of excretory-secretory antigens against acute toxoplasmosis in murine model","volume":"225","author":"Gaafar","year":"2022","journal-title":"Acta Trop."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"127228","DOI":"10.1016\/j.ijbiomac.2023.127228","article-title":"Immunomodulatory chitosan nanoparticles for Toxoplasma gondii infection: Novel application of chitosan in complex propranolol-hydrochloride as an adjuvant in vaccine delivery","volume":"253","author":"Khorshidvand","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.ijbiomac.2022.03.146","article-title":"Novel naltrexone hydrochloride nanovaccine based on chitosan nanoparticles promotes induction of Th1 and Th17 immune responses resulting in protection against Toxoplasma gondii tachyzoites in a mouse model","volume":"208","author":"Khorshidvand","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lee, D.H., Lee, S.H., Kim, A.R., and Quan, F.S. (2024). Correction: Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0301214"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Heo, S.I., Kang, H.J., Mao, J., Yang, Z.S., Ahmed, M.A., and Quan, F.S. (2025). Protective Efficacy Induced by Virus-like Particles Expressing Dense Granule Protein 5 of Toxoplasma gondii. Vaccines, 13.","DOI":"10.3390\/vaccines13080787"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1080\/17435889.2025.2546769","article-title":"Influenza virus-like particles presenting Toxoplasma gondii dense granule protein 7 protect mice from lethal ME49 challenge","volume":"20","author":"Mao","year":"2025","journal-title":"Nanomedicine"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kang, H.J., and Quan, F.S. (2025). Efficacy of Heterologous Vaccination Using Virus-Like Particles and Vaccinia Virus Containing MIC8 and AMA1 Proteins of Toxoplasma gondii. Vaccines, 13.","DOI":"10.3390\/vaccines13080862"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108900","DOI":"10.1016\/j.exppara.2025.108900","article-title":"Protection induced by recombinant vaccinia virus targeting the ROP4 of Toxoplasma gondii in mice","volume":"269","author":"Yoon","year":"2025","journal-title":"Exp. Parasitol."},{"key":"ref_77","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"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Huang, C., Bai, S., Yu, H., Pan, M., Hou, Z., Fu, L., and Huang, S. (2025). Colloidal Manganese Salt Improves the Efficacy of Toxoplasma gondii Inactivated Vaccine in Mice. Vaccines, 13.","DOI":"10.3390\/vaccines13121230"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Bai, S.Y., Zhou, G.Q., Li, Y.Y., Pan, M., Fu, L., and Huang, S.Y. (2025). High Levels of Protection Against Acute and Chronic Toxoplasmosis in Institute of Cancer Research Mice with a Novel Low-Temperature Inactivated Toxoplasma gondii Candidate Vaccine Adjuvanted with HA201\/HA203. Foodborne Pathog. Dis., fpd20240159.","DOI":"10.1089\/fpd.2024.0159"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e00269","DOI":"10.1016\/j.fawpar.2025.e00269","article-title":"Design and immunological evaluation of a multi-epitope vaccine candidate against Toxoplasma gondii incorporating MIC13, GRA1, and SAG1 antigens in BALB\/c mice","volume":"40","author":"Hosseininejad","year":"2025","journal-title":"Food Waterborne Parasitol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Said, D.E., Amer, E.I., Sheta, E., Makled, S., Diab, H.E., and Arafa, F.M. (2022). Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7120401"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Said, D.E., Amer, E.I., Sheta, E., Makled, S., Arafa, F.M., and Diab, H.E. (2023). Nano-Encapsulated Antioxidant: Retinoic Acid as a Natural Mucosal Adjuvant for Intranasal Immunization against Chronic Experimental Toxoplasmosis. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8020106"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"122199","DOI":"10.1016\/j.ijpharm.2022.122199","article-title":"Development of multistage recombinant protein vaccine formulations against toxoplasmosis using a new chitosan and porin based adjuvant system","volume":"626","author":"Karakavuk","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"107812","DOI":"10.1016\/j.actatropica.2025.107812","article-title":"Recombinant vaccinia virus expressing MIC8, AMA1, or RON4 induce protection against Toxoplasma gondii ME49 strain infection","volume":"270","author":"Kang","year":"2025","journal-title":"Acta Trop."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","unstructured":"Sun, H.C., Yuan, X.F., Zhou, W., Zhou, Z.J., Su, F., Fu, Y., Hao, L.L., Liu, X., Zhou, X., and Ye, S.Y. (2025). Bacillus subtilis spores displaying Toxoplasma gondii GRA12 induce immunity against acute toxoplasmosis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1457560"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"109024","DOI":"10.1016\/j.exppara.2025.109024","article-title":"Niosomes as a vehicle for excretory\/secretory antigens enhance immunization efficacy of Toxoplasma gondii vaccine","volume":"277","author":"Younis","year":"2025","journal-title":"Exp. Parasitol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"107041","DOI":"10.1016\/j.actatropica.2023.107041","article-title":"Protective efficacy of Toxoplasma gondii infected cells-derived exosomes against chronic murine toxoplasmosis","volume":"248","author":"Tawfeek","year":"2023","journal-title":"Acta Trop."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Li, L., Guan, Y.C., Bai, S.Y., Jin, Q.W., Tao, J.P., Zhu, G.D., and Huang, S.Y. (2023). Mineralization Reduces the Toxicity and Improves Stability and Protective Immune Response Induced by Toxoplasma gondii. Vaccines, 12.","DOI":"10.3390\/vaccines12010035"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e2219533120","DOI":"10.1073\/pnas.2219533120","article-title":"Invasion of Toxoplasma gondii bradyzoites: Molecular dissection of the moving junction proteins and effective vaccination targets","volume":"120","author":"Najm","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.pt.2011.03.009","article-title":"Innate responses to Toxoplasma gondii in mice and humans","volume":"27","author":"Pifer","year":"2011","journal-title":"Trends Parasitol."},{"key":"ref_92","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_93","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_94","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1080\/21645515.2021.1934354","article-title":"Adjuvants: Friends in vaccine formulations against infectious diseases","volume":"17","author":"Tuero","year":"2021","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sun, H.C., Huang, J., Fu, Y., Hao, L.L., Liu, X., and Shi, T.Y. (2021). Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.787635"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1016\/j.vaccine.2019.05.083","article-title":"Vaccination challenges and strategies against long-lived Toxoplasma gondii","volume":"37","author":"Loh","year":"2019","journal-title":"Vaccine"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Yang, J., Nie, L., Song, Y., Yang, Z., Yang, L., Ren, H., Li, W., Mahmmod, Y., Zhang, X.X., and Yuan, Z. (2025). Immunogenicity and Protective Efficacy of a Recombinant Toxoplasma gondii GRA12 Vaccine in Domestic Cats. Vaccines, 13.","DOI":"10.3390\/vaccines13080851"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13567-025-01645-2","article-title":"An inactivated vaccine against acquired Toxoplasma gondii infection in pigs as a tool to minimize the zoonotic transmission risk","volume":"56","author":"Ferre","year":"2025","journal-title":"Vet. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1089\/fpd.2024.0060","article-title":"Pru\u0394cdpk2 Protects Pigs Against Acute Toxoplasmosis Depending on T-Lymphocyte Subsets and Natural Killer Cell Responses","volume":"21","author":"Fan","year":"2024","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"107540","DOI":"10.1016\/j.actatropica.2025.107540","article-title":"Immunization with plant-based vaccine expressing Toxoplasma gondii SAG1 fused to plant HSP90 elicits protective immune response in lambs","volume":"262","author":"Campero","year":"2025","journal-title":"Acta Trop."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"105454","DOI":"10.1016\/j.jprot.2025.105454","article-title":"Detection and identification of highly antigenic proteins from cytoskeleton of Toxoplasma gondii by immune-proteomics","volume":"317","author":"Carranza","year":"2025","journal-title":"J. Proteom."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e70004","DOI":"10.1111\/pim.70004","article-title":"Toxoplasma gondii (GRA10): A Closer Glance Into Immunogenic and Biochemical Characteristics Using In Silico Approach","volume":"47","author":"Ghaffari","year":"2025","journal-title":"Parasite Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3514414","DOI":"10.1155\/japr\/3514414","article-title":"In Silico-Based Investigation of the Immunogenicity and Biochemical Attributes of Toxoplasma gondii Apical Membrane Antigen 1 (TgAMA1)","volume":"2025","author":"Foroutan","year":"2025","journal-title":"J. Parasitol. Res."},{"key":"ref_104","first-page":"103475","article-title":"In silico analysis and structural vaccinology prediction of Toxoplasma gondii ROP41 gene via immunoinformatics methods as a vaccine candidate","volume":"73","author":"Asadi","year":"2025","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Majidiani, H., Pourseif, M.M., Kordi, B., Sadeghi, M.R., and Najafi, A. (2024). TgVax452, an epitope-based candidate vaccine targeting Toxoplasma gondii tachyzoite-specific SAG1-related sequence (SRS) proteins: Immunoinformatics, structural simulations and experimental evidence-based approaches. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09807-x"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s13071-022-05497-z","article-title":"Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins","volume":"15","author":"Li","year":"2022","journal-title":"Parasit. Vectors"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/5\/437\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:49:16Z","timestamp":1777538956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/5\/437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":106,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["vetsci13050437"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13050437","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}