{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:19Z","timestamp":1787029999537,"version":"build-2736575974"},"reference-count":93,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Melatonin (MLT) is now emerging as one of the universally accepted immunostimulators with broad applications in medicine. It is a biological manipulator of the immune system, including mucosal ones. MLT was encapsulated in solid lipid nanoparticles (SLNs), then 100 mg\/kg\/dose of MLT-SLNs was used as an adjuvant of Toxoplasma lysate antigen (TLA). Experimental mice were intra-nasally inoculated with three doses of different regimens every two weeks, then challenged with 20 cysts of T. gondii Me49 strain, where they were sacrificed four weeks post-infection. Protective vaccine efficacy was evident via the significant brain cyst count reduction of 58.6%, together with remarkably high levels of humoral systemic and mucosal anti-Toxoplasma antibodies (Ig G, Ig A), supported by a reduced tachyzoites invasion of Vero cells in vitro upon incubation with sera obtained from these vaccinated mice. A cellular immune response was evident through the induction of significant levels of interferon-gamma (IFN \u03b3), associated with morphological deteriorations of cysts harvested from the brains of vaccinated mice. Furthermore, the amelioration of infection-induced oxidative stress (OS) and histopathological changes were evident in mice immunized with TLA\/MLT-SLNs. In conclusion, the present study highlighted the promising role of intranasal MLT-SLNs as a novel mucosal adjuvant candidate against chronic toxoplasmosis.<\/jats:p>","DOI":"10.3390\/tropicalmed7120401","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:56:25Z","timestamp":1669611385000},"page":"401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nano-Encapsulated Melatonin: A Promising Mucosal Adjuvant in Intranasal Immunization against Chronic Experimental T. gondii Infection"],"prefix":"10.3390","volume":"7","author":[{"given":"Doaa E.","family":"Said","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria 5424041, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eglal I.","family":"Amer","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria 5424041, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-5229","authenticated-orcid":false,"given":"Eman","family":"Sheta","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria 5424041, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Makled","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala E.","family":"Diab","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria 5424041, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-3193","authenticated-orcid":false,"given":"Fadwa M.","family":"Arafa","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria 5424041, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.pt.2020.08.005","article-title":"Toxoplasma gondii: An Underestimated Threat?","volume":"36","author":"Milne","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/cid\/cis508","article-title":"Foodborne Toxoplasmosis","volume":"55","author":"Jones","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.3389\/fmicb.2019.01875","article-title":"Immunization with a Live-Attenuated RH:\u0394NPT1 Strain of Toxoplasma gondii Induces Strong Protective Immunity Against Toxoplasmosis in Mice","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.imlet.2008.11.009","article-title":"Principles of vaccination and possible development strategies for rational design","volume":"122","author":"Boog","year":"2009","journal-title":"Immunol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1348-0421.2005.tb03656.x","article-title":"Protective Effect of Vaccination with Toxoplasma lysate Antigen and CpG as an Adjuvant against Toxoplasma gondii in Susceptible C57BL\/6 Mice","volume":"49","author":"Shaohong","year":"2005","journal-title":"Microbiol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wagner, A., Schabussova, I., Ruttkowski, B., Peschke, R., Kur, J., Kundi, M., Joachim, A., and Wiedermann, U. (2015). Prime-Boost Vaccination with Toxoplasma Lysate Antigen, but Not with a Mixture of Recombinant Protein Antigens, Leads to Reduction of Brain Cyst Formation in BALB\/c Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126334"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1007\/s00436-014-3882-0","article-title":"Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: Comparison of immune responses in intranasal versus intramuscular administrations","volume":"113","author":"Mohamed","year":"2014","journal-title":"Parasitol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0304-4017(03)00044-X","article-title":"Immune responses against excreted\/secreted antigens of Toxoplasma gondii tachyzoites in the murine model","volume":"113","author":"Daryani","year":"2003","journal-title":"Vet. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1586\/14760584.2015.1081067","article-title":"Effect of vaccine administration modality on immunogenicity and efficacy","volume":"14","author":"Zhang","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.vaccine.2011.11.003","article-title":"New insights in mucosal vaccine development","volume":"30","author":"Pavot","year":"2012","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"978","DOI":"10.4161\/hv.6.12.13142","article-title":"Mucosal immunization: A realistic alternative","volume":"6","author":"Otczyk","year":"2010","journal-title":"Hum. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lewis, D.J.M., Huo, Z., Barnett, S., Kromann, I., Giemza, R., Galiza, E., Woodrow, M., Thierry-Carstensen, B., Andersen, P., and Novicki, D. (2009). Transient Facial Nerve Paralysis (Bell\u2019s Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006999"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1136\/gut.51.5.634","article-title":"Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers","volume":"51","author":"Banerjee","year":"2002","journal-title":"Gut"},{"key":"ref_15","first-page":"289597","article-title":"Cytokines: The Future of Intranasal Vaccine Adjuvants","volume":"2011","author":"Thompson","year":"2011","journal-title":"J. Immunol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s10787-017-0393-5","article-title":"Immunomodulatory basis of antioxidant therapy and its future prospects: An appraisal","volume":"25","author":"Ajith","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.yhbeh.2018.08.006","article-title":"The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior","volume":"105","author":"Battagello","year":"2018","journal-title":"Horm. Behav."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.vaccine.2009.01.001","article-title":"Melatonin enhances the immune response to vaccination against A1 and C strains of Dichelobacter nodosus","volume":"27","author":"Ramos","year":"2009","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1177\/00912700022009422","article-title":"The absolute bioavailability of oral melatonin","volume":"40","author":"Nafziger","year":"2000","journal-title":"J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ijpharm.2009.07.001","article-title":"Melatonin-loaded lecithin\/chitosan nanoparticles: Physicochemical characterisation and permeability through Caco-2 cell monolayers","volume":"381","author":"Hafner","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0939-6411(00)00087-4","article-title":"Solid lipid nanoparticles (SLN) for controlled drug delivery\u2014A review of the state of the art","volume":"50","author":"Gohla","year":"2000","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1128\/AAC.45.6.1771-1779.2001","article-title":"Atovaquone Nanosuspensions Show Excellent Therapeutic Effect in a New Murine Model of Reactivated Toxoplasmosis","volume":"45","author":"Krause","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ijpharm.2016.12.026","article-title":"Nebulized solid lipid nanoparticles for the potential treatment of pulmonary hypertension via targeted delivery of phosphodiesterase-5-inhibitor","volume":"517","author":"Makled","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Eissa, M.M., El-Moslemany, R.M., Ramadan, A.A., Amer, E.I., El-Azzouni, M.Z., and El-Khordagui, L.K. (2015). Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141788"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.colsurfb.2010.11.037","article-title":"Physicochemical properties of nevirapine-loaded solid lipid nanoparticles and nanostructured lipid carriers","volume":"83","author":"Kuo","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.colsurfb.2012.05.006","article-title":"Preparation and stability study of norfloxacin-loaded solid lipid nanoparticle suspensions","volume":"98","author":"Wang","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00705-017-3647-z","article-title":"Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells","volume":"163","author":"Mohebbi","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shirai, S., Kawai, A., Shibuya, M., Munakata, L., Omata, D., Suzuki, R., and Yoshioka, Y. (2020). Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses. Vaccines, 8.","DOI":"10.3390\/vaccines8030433"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.actatropica.2015.07.013","article-title":"Homologous prime-boost strategy with TgPI-1 improves the immune response and protects highly susceptible mice against chronic Toxoplasma gondii infection","volume":"150","author":"Fenoy","year":"2015","journal-title":"Acta Trop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.exppara.2015.06.005","article-title":"Could miltefosine be used as a therapy for toxoplasmosis?","volume":"157","author":"Eissa","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A simple method for clinical assay of superoxide dismutase","volume":"34","author":"Sun","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0076-6879(90)86135-I","article-title":"Malondialdehyde determination as index of lipid peroxidation","volume":"186","author":"Draper","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.7243\/2055-091X-1-5","article-title":"Past, present and future: Overview on histology and histopathology","volume":"1","author":"Musumeci","year":"2014","journal-title":"J. Histol. Histopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.3389\/fmicb.2020.01526","article-title":"Impact of Vaccines; Health, Economic and Social Perspectives","volume":"11","author":"Rodrigues","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_37","first-page":"7163","article-title":"The new era of vaccines: The \u201cnanovaccinology\u201d","volume":"23","author":"Visalli","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"00020","DOI":"10.15406\/ijvv.2016.02.00020","article-title":"Antioxidants and Vaccines","volume":"2","author":"Gowder","year":"2016","journal-title":"Int. J. Vaccines Vaccin."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20140145","DOI":"10.1098\/rstb.2014.0145","article-title":"Potential for use of retinoic acid as an oral vaccine adjuvant","volume":"370","author":"Kelly","year":"2015","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y.-X., Yang, G.-H., Zhang, L.-L., Wang, J., and Wang, J.-F. (2021). Melatonin as Immune Potentiator for Enhancing Subunit Vaccine Efficacy against Bovine Viral Diarrhea Virus. Vaccines, 9.","DOI":"10.3390\/vaccines9091039"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3797\/scipharm.1011-05","article-title":"Amoxicillin Loaded Chitosan\u2013Alginate Polyelectrolyte Complex Nanoparticles as Mucopenetrating Delivery System for H. Pylori","volume":"79","author":"Arora","year":"2011","journal-title":"Sci. Pharm."},{"key":"ref_42","first-page":"17","article-title":"Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design","volume":"10","author":"Emami","year":"2015","journal-title":"Res. Pharm. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1208\/s12249-009-9287-1","article-title":"Formulation and Evaluation of Lidocaine Lipid Nanosystems for Dermal Delivery","volume":"10","author":"Pathak","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejpb.2018.03.004","article-title":"Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity\u2014Optimization of nicotine loading efficiency","volume":"128","author":"Ding","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00396-010-2341-4","article-title":"The temperature effect on electrokinetic properties of the silica\u2013polyvinyl alcohol (PVA) system","volume":"289","year":"2011","journal-title":"Colloid Polym. Sci."},{"key":"ref_46","first-page":"1","article-title":"Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line","volume":"784\u2013785","author":"Baierle","year":"2015","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1159\/000489667","article-title":"Melatonin Loading Chitosan-Tripolyphosphate Nanoparticles: Application in Attenuating Etoposide-Induced Genotoxicity in HepG2 Cells","volume":"102","author":"Shokrzadeh","year":"2018","journal-title":"Pharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.addr.2011.05.017","article-title":"Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles","volume":"63","author":"Cai","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1208\/s12249-010-9414-z","article-title":"Development and statistical optimization of solid lipid nanoparticles of simvastatin by using 2(3) full-factorial design","volume":"11","author":"Shah","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"216","DOI":"10.4103\/0975-1483.83765","article-title":"Formulation and evaluation of solid lipid nanoparticles of ramipril","volume":"3","author":"Ekambaram","year":"2011","journal-title":"J. Young Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"363404","DOI":"10.1155\/2014\/363404","article-title":"Enhanced oral bioavailability of efavirenz by solid lipid nanoparticles: In vitro drug release and pharmacokinetics studies","volume":"2014","author":"Gaur","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1248\/cpb.58.650","article-title":"Formulation and evaluation of solid lipid nanoparticles of a water soluble drug: Zidovudine","volume":"58","author":"Singh","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1080\/14760584.2019.1604231","article-title":"Selection of adjuvants for vaccines targeting specific pathogens","volume":"18","author":"Sarkar","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Costa, C.P.B.S., Moreira, J.N., Silva, R., Almeida, H., Sousa Lobo, J.M., and Silva, A.C. (2021). In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN). Pharmaceuticals, 14.","DOI":"10.3390\/ph14080711"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4","DOI":"10.7774\/cevr.2019.8.1.4","article-title":"Rhoptry antigens as Toxoplasma gondii vaccine target","volume":"8","author":"Foroutan","year":"2019","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_56","first-page":"23","article-title":"Current progress toward vaccines against Toxoplasma gondii","volume":"4","author":"Garcia","year":"2014","journal-title":"Vaccine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1586\/erv.11.21","article-title":"Trends in vaccine adjuvants","volume":"10","author":"Schijns","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2010.09.013","article-title":"Vaccination strategies to promote mucosal antibody responses","volume":"33","author":"Chen","year":"2010","journal-title":"Immunity"},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.4049\/jimmunol.150.9.3951","article-title":"Antibodies to Toxoplasma gondii major surface protein (SAG-1, P30) inhibit infection of host cells and are produced in murine intestine after peroral infection","volume":"150","author":"Mineo","year":"1993","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1128\/IAI.68.3.1026-1033.2000","article-title":"B Cells Are Essential for Vaccination-Induced Resistance to Virulent Toxoplasma gondii","volume":"68","author":"Sayles","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1051\/parasite\/2017013","article-title":"Vaccination with recombinant adenovirus expressing multi-stage antigens of Toxoplasma gondii by the mucosal route induces higher systemic cellular and local mucosal immune responses than with other vaccination routes","volume":"24","author":"Wang","year":"2017","journal-title":"Parasite"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.4049\/jimmunol.161.5.2168","article-title":"Peripheral immune tolerance blocks clonal expansion but fails to prevent the differentiation of Th1 cells","volume":"161","author":"Malvey","year":"1998","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1080\/21505594.2021.2012346","article-title":"The pathogenicity and virulence of Toxoplasma gondii","volume":"12","author":"Sanchez","year":"2021","journal-title":"Virulence"},{"key":"ref_65","first-page":"57","article-title":"Genetic analysis of the diversity in Toxoplasma gondii","volume":"40","year":"2004","journal-title":"Ann. Ist. Super Sanita."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Regod\u00f3n, S.R.A., M\u00edguez, M.P., Carrillo-Vico, A., Rosado, J.A., and Jard\u00edn, I. (2012). Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep. BMC Vet. Res., 8.","DOI":"10.1186\/1746-6148-8-84"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.3389\/fmicb.2018.02965","article-title":"Protective Efficacy Against Acute and Chronic Toxoplasma gondii Infection Induced by Immunization With the DNA Vaccine TgDOC2C","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.4049\/jimmunol.0900640","article-title":"Early Response of Mucosal Epithelial Cells during Toxoplasma gondii Infection","volume":"183","author":"Ju","year":"2009","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1074-7613(03)00122-5","article-title":"Anti-Inflammatory Role for Intracellular Dimeric Immunoglobulin A by Neutralization of Lipopolysaccharide in Epithelial Cells","volume":"18","author":"Fernandez","year":"2003","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/mi.2007.6","article-title":"The immune geography of IgA induction and function","volume":"1","author":"MacPherson","year":"2007","journal-title":"Mucosal Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1749-6632.2011.06266.x","article-title":"Regulation of mucosal IgA responses: Lessons from primary immunodeficiencies","volume":"1238","author":"Cerutti","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.vaccine.2011.10.093","article-title":"A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging","volume":"30","author":"Asanuma","year":"2012","journal-title":"Vaccine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.1128\/IAI.71.9.5254-5265.2003","article-title":"Protective Mucosal Th2 Immune Response against Toxoplasma gondii by Murine Mesenteric Lymph Node Dendritic Cells","volume":"71","author":"Aline","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2020.03.020","article-title":"Advancements in prophylactic and therapeutic nanovaccines","volume":"108","author":"Bhardwaj","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nri3598","article-title":"Innate immunity to Toxoplasma gondii infection","volume":"14","author":"Yarovinsky","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1128\/CMR.00005-17","article-title":"Toxoplasma Effectors Targeting Host Signaling and Transcription","volume":"30","author":"Hakimi","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Martens, S., Parvanova, I., Zerrahn, J., Griffiths, G., Schell, G., Reichmann, G., and Howard, J.C. (2005). Disruption of Toxoplasma gondii Parasitophorous Vacuoles by the Mouse p47-Resistance GTPases. PLoS Pathog., 1.","DOI":"10.1371\/journal.ppat.0010024"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"243796","DOI":"10.1155\/2011\/243796","article-title":"CD8 T Cells and Toxoplasma gondii: A New Paradigm","volume":"2011","author":"Gigley","year":"2011","journal-title":"J. Parasitol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.ajpath.2019.04.018","article-title":"Penetration of CD8(+) Cytotoxic T Cells into Large Target, Tissue Cysts of Toxoplasma gondii, Leads to Its Elimination","volume":"189","author":"Tiwari","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8045969","DOI":"10.1155\/2016\/8045969","article-title":"Blood Levels of Oxidant\/Antioxidant Parameters in Rats Infected with Toxoplasma gondii","volume":"2016","author":"Bahrami","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"24438","DOI":"10.3390\/ijms141224438","article-title":"Oxidative Stress and Neurodegenerative Disorders","volume":"14","author":"Li","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.3390\/ijms14048638","article-title":"Melatonin: Buffering the Immune System","volume":"14","author":"Lardone","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Contreras, M., Rubio, C.P., De La Fuente, J., Villar, M., Merino, O., Gualito, J.M., and Cer\u00f3n, J.J. (2020). Changes in Serum Biomarkers of Oxidative Stress in Cattle Vaccinated with Tick Recombinant Antigens: A Pilot Study. Vaccines, 9.","DOI":"10.3390\/vaccines9010005"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1600-079X.2005.00248.x","article-title":"A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes","volume":"39","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_85","first-page":"241","article-title":"Acute toxoplasmosis and antioxidant levels in the liver, kidney and brain of rats","volume":"64","author":"Yaman","year":"2018","journal-title":"Ann. Parasitol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0079-6123(08)63259-8","article-title":"Evaluation of the concomitance of lipid peroxidation in experimental models of cerebral ischemia and stroke","volume":"96","author":"Watson","year":"1993","journal-title":"Prog. Brain Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1248\/bpb.b17-00026","article-title":"Antioxidative Protection of Squalene Adjuvant and Rabies Vaccine with Adjuvant","volume":"40","author":"Ondrejkova","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3347\/kjp.2008.46.4.293","article-title":"Malondialdehyde, glutathione, and nitric oxide levels in Toxoplasma gondii seropositive patients","volume":"46","author":"Karaman","year":"2008","journal-title":"Korean J. Parasitol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"105150","DOI":"10.1016\/j.meegid.2021.105150","article-title":"Evaluation of Th17 immune responses of recombinant DNA vaccine encoding GRA14 and ROP13 genes against Toxoplasma gondii in BALB\/c mice","volume":"96","author":"Fatollahzadeh","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105210","DOI":"10.1016\/j.phrs.2020.105210","article-title":"Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis","volume":"161","author":"Morvaridzadeh","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.1007\/s12035-016-0297-1","article-title":"Inflammatory Response in the CNS: Friend or Foe?","volume":"54","author":"Sochocka","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1177\/0394632016638668","article-title":"Role of oxidative stress in the pathophysiology of Toxoplasma gondii infection","volume":"29","author":"Dincel","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0896-6273(95)90287-2","article-title":"Superoxide dismutase delays neuronal apoptosis: A role for reactive oxygen species in programmed neuronal death","volume":"14","author":"Greenlund","year":"1995","journal-title":"Neuron"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/401\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:28:01Z","timestamp":1760146081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,27]]},"references-count":93,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["tropicalmed7120401"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed7120401","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,27]]}}}