{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:17:38Z","timestamp":1777943858729,"version":"3.51.4"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic>, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of <jats:italic>T. gondii<\/jats:italic> GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic <jats:italic>T. gondii<\/jats:italic> infection was assessed by observing the survival time after challenge with the highly virulent <jats:italic>T. gondii<\/jats:italic> RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of <jats:italic>T. gondii<\/jats:italic> (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-\u03b3, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4\u2013 T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-\u03b21, IL-1\u03b2, and the transcription factor factors ROR\u03b3t, ROR\u03b1, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (<jats:italic>p<\/jats:italic> &amp;gt; 0.05). These effective immune responses had mounted protective immunity against <jats:italic>T. gondii<\/jats:italic> infection, with a prolonged survival time (16.80 \u00b1 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic <jats:italic>T. gondii<\/jats:italic> infection.<\/jats:p>","DOI":"10.3389\/fmicb.2021.630682","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T08:06:06Z","timestamp":1619597166000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Immunization With a DNA Vaccine Encoding the Toxoplasma gondii\u2019 s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuchao","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cellimm.2016.07.004","article-title":"Role of pro-inflammatory cytokine IL-17 in Leishmania pathogenesis and in protective immunityby Leishmania vaccines.","volume":"309","author":"Banerjee","year":"2016","journal-title":"Cell Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1016\/j.vaccine.2009.01.022","article-title":"Exosomes are an effective vaccine against congenital toxoplasmosis in mice.","volume":"27","author":"Beauvillain","year":"2009","journal-title":"Vaccine"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005902","article-title":"Th17 cells are more protective than Th1 cells against the intracellular parasite Trypanosoma cruzi.","volume":"12","author":"Cai","year":"2016","journal-title":"PLoS Pathog."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6757","DOI":"10.1016\/j.vaccine.2015.10.077","article-title":"Toxoplasma gondii: vaccination with a DNA vaccine encoding T- and B-cell epitopes of SAG1, GRA2, GRA7 and ROP16 elicits protection against acute toxoplasmosis in mice.","volume":"33","author":"Cao","year":"2015","journal-title":"Vaccine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"6225","DOI":"10.1016\/j.vaccine.2013.10.034","article-title":"DNA immunization with eukaryotic initiation factor-2\u03b1 of Toxoplasma gondii induces protective immunity against acute and chronic toxoplasmosis in mice.","volume":"31","author":"Chen","year":"2013","journal-title":"Vaccine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1586\/14760584.2015.1011133","article-title":"DNA vaccination with genes encoding Toxoplasma gondii antigens ROP5 and GRA15 induces protective immunity against toxoplasmosis in Kunming mice.","volume":"14","author":"Chen","year":"2015","journal-title":"Expert. 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