{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T02:17:32Z","timestamp":1782440252866,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31802180"],"award-info":[{"award-number":["31802180"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The International Science and Technology Cooperation Project of Gansu Provincial Key Research and Development Program","award":["17JR7WA031"],"award-info":[{"award-number":["17JR7WA031"]}]},{"name":"The Elite Program of Chinese Academy of Agricultural Sciences and the Agricultural Science and Technology Innovation Program (ASTIP)","award":["CAAS-ASTIP-2016-LVRI-03"],"award-info":[{"award-number":["CAAS-ASTIP-2016-LVRI-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>In the present study, a dense granule protein 17 (gra17) and novel putative transporter (npt1) double deletion mutant of Toxoplasma gondii RH strain was engineered. The protective efficacy of vaccination using RH\u0394gra17\u0394npt1 tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RH\u0394gra17\u0394npt1 induced a strong humoral and cellular response, as indicated by the increased levels of anti-T. gondii specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-\u03b3). Vaccinated mice were protected against a lethal challenge dose (103 tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 T. gondii Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that T. gondii RH\u0394gra17\u0394npt1 mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis by balancing inflammatory response with immunogenicity.<\/jats:p>","DOI":"10.3390\/microorganisms8030352","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T06:34:23Z","timestamp":1583130863000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["RH\u0394gra17\u0394npt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice"],"prefix":"10.3390","volume":"8","author":[{"given":"Qin-Li","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xiu","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-930X","authenticated-orcid":false,"given":"Hany M.","family":"Elsheikha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Zhen","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Bi","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao-Shan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-4628","authenticated-orcid":false,"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"},{"name":"Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University College of Veterinary Medicine, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/CMR.05013-11","article-title":"Epidemiology of and diagnostic strategies for toxoplasmosis","volume":"25","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0020-7519(00)00140-5","article-title":"Recent trends in research on congenital toxoplasmosis","volume":"31","author":"Petersen","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.1016\/j.jinf.2013.09.023","article-title":"It is not only the cat that did it: How to prevent and treat congenital toxoplasmosis","volume":"68","year":"2014","journal-title":"J. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/S2352-3018(17)30005-X","article-title":"Prevalence and burden of Toxoplasma gondii infection in HIV-infected people: A systematic review and meta-analysis","volume":"4","author":"Wang","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/j.1469-0691.2006.01444.x","article-title":"Toxoplasma gondii infection in pregnancy: Opportunities and pitfalls of serological diagnosis","volume":"12","author":"Sensini","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2147\/DDDT.S60973","article-title":"Drugs in development for toxoplasmosis: Advances, challenges, and current status","volume":"11","author":"Holland","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1136\/vr.129.5.89","article-title":"Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant","volume":"129","author":"Buxton","year":"1991","journal-title":"Vet. Rec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1017\/S0031182014000481","article-title":"Veterinary vaccines against toxoplasmosis","volume":"141","author":"Gatkowska","year":"2014","journal-title":"Parasitology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1586\/14760584.2015.1098539","article-title":"Recent advances in developing vaccines against Toxoplasma gondii: An update","volume":"14","author":"Zhang","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"730","DOI":"10.3389\/fimmu.2017.00730","article-title":"Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice","volume":"8","author":"Wang","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1093\/infdis\/jiy211","article-title":"Live attenuated Pru: \u0394cdpk2 strain of Toxoplasma gondii protects against acute, chronic, and congenital toxoplasmosis","volume":"218","author":"Wang","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.chom.2015.04.003","article-title":"The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole","volume":"17","author":"Gold","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.pt.2014.12.002","article-title":"Toxoplasma secretory granules: One population or more?","volume":"31","author":"Mercier","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14455","DOI":"10.1038\/ncomms14455","article-title":"Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites","volume":"8","author":"Rajendran","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_18","first-page":"9","article-title":"Measurement and analysis of the reproductive performance in six commonly used SPF mice and rats","volume":"10","author":"Sun","year":"2016","journal-title":"Chin. J. Comp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0091-679X(08)61845-2","article-title":"Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii","volume":"45","author":"Roos","year":"1994","journal-title":"Methods Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.3389\/fmicb.2018.02316","article-title":"Differential brain MicroRNA expression profiles after acute and chronic infection of mice with Toxoplasma gondii oocysts","volume":"9","author":"Hu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_21","first-page":"e1420","article-title":"Obtaining highly purified Toxoplasma gondii oocysts by a discontinuous cesium chloride gradient","volume":"33","author":"Staggs","year":"2009","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1096\/fj.201901416RR","article-title":"Novel roles of dense granule protein 12 (GRA12) in Toxoplasma gondii infection","volume":"34","author":"Wang","year":"2020","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E6956","DOI":"10.1073\/pnas.1722202115","article-title":"Human impact on the diversity and virulence of the ubiquitous zoonotic parasite Toxoplasma gondii","volume":"115","author":"Shwab","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","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_25","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_26","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_27","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_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fimmu.2016.00347","article-title":"Comparative analysis of conventional natural killer cell responses to acute infection with Toxoplasma gondii strains of different virulence","volume":"7","author":"Ivanova","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"798","DOI":"10.4049\/jimmunol.157.2.798","article-title":"In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha","volume":"157","author":"Gazzinelli","year":"1996","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0140-6736(07)60072-5","article-title":"Effectiveness of prenatal treatment for congenital toxoplasmosis: A meta-analysis of individual patients\u2019 data","volume":"369","author":"Group","year":"2007","journal-title":"Lancet"},{"key":"ref_31","first-page":"120","article-title":"Modulators of the balance between M1 and M2 macrophages during pregnancy","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.micpath.2015.10.002","article-title":"IL-10 regulate decidual Tregs apoptosis contributing to the abnormal pregnancy with Toxoplasma gondii infection","volume":"89","author":"Lao","year":"2015","journal-title":"Microb. Pathog."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/3\/352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:03:08Z","timestamp":1760173388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/3\/352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,1]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["microorganisms8030352"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms8030352","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,1]]}}}