{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:41:04Z","timestamp":1779147664872,"version":"3.51.4"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030061"],"award-info":[{"award-number":["82030061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Projects of China","award":["2018YFA0507300"],"award-info":[{"award-number":["2018YFA0507300"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["24614018"],"award-info":[{"award-number":["24614018"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["26461370"],"award-info":[{"award-number":["26461370"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["15H02903"],"award-info":[{"award-number":["15H02903"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MEXT-Supported Program for Strategic Founding of Research in Private Universities","award":["S1201007"],"award-info":[{"award-number":["S1201007"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Schistosomiasis is one of the most important neglected tropical infectious diseases to overcome and the primary cause of its pathogenesis is ectopic maturation of the parasite eggs. Uptake of cholesteryl ester from the host high-density lipoprotein (HDL) is a key in this process in <jats:italic>Schistosoma japonicum<\/jats:italic> and CD36-related protein (CD36RP) has been identified as the receptor for this reaction. Antibody against the extracellular domain of CD36RP (Ex160) efficiently blocked the HDL cholesteryl ester uptake and the egg embryonation <jats:italic>in vitro<\/jats:italic>. However, whether Ex160 immunization could efficiently raise proper antibody responses to sufficiently block HDL cholesteryl ester uptake and the egg embryonation to protect host <jats:italic>in vivo<\/jats:italic> is very interesting but unknown.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p>In this study, rabbits were immunized with the recombinant Ex160 peptide (rEx160) to evaluate its anti-pathogenic vaccine potential. Immunization with rEx160 induced consistent anti-Ex160 IgG antibody and significant reduction in development of the liver granulomatosis lesions associated with suppressed intrahepatic maturation of the schistosome eggs. The immunization with rEx160 rescued reduction of serum HDL by the infection without changing its size distribution, being consistent with interference of the HDL lipid uptake by the parasites or their eggs by antibody against Ex160 in <jats:italic>in vitro<\/jats:italic> culture.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>The results demonstrated that vaccination strategy against nutritional supply pathway of the parasite is effective for reducing its pathogenesis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011749","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T18:26:20Z","timestamp":1701282380000},"page":"e0011749","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vaccination against the HDL receptor of S. japonicum inhibits egg embryonation and prevents fatal hepatic complication in rabbit model"],"prefix":"10.1371","volume":"17","author":[{"given":"Jifeng","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zechao","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zil\u00fce","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuniko","family":"Okumura-Noji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-2428","authenticated-orcid":true,"given":"Chuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"pntd.0011749.ref001","article-title":"Who_Fact_Sheet WHO","journal-title":"Schistosomiasis Fact Sheet"},{"key":"pntd.0011749.ref002","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.3389\/fimmu.2018.02492","article-title":"Schistosoma \u201ceggs-iting\u201d the host: granuloma formation and egg excretion.","volume":"9","author":"C Schwartz","year":"2018","journal-title":"Frontiers in immunology"},{"issue":"4","key":"pntd.0011749.ref003","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1111\/brv.12708","article-title":"Changing our view of the Schistosoma granuloma to an ecological standpoint.","volume":"96","author":"KK Malta","year":"2021","journal-title":"Biological Reviews."},{"issue":"1","key":"pntd.0011749.ref004","first-page":"13","article-title":"Schistosomiasis (primer).","volume":"4","author":"DP McManus","year":"2018","journal-title":"Nature Reviews: Disease Primers."},{"issue":"Pt 3","key":"pntd.0011749.ref005","first-page":"329","article-title":"The schistosome egg: development and secretions","volume":"122","author":"PD Ashton","year":"2001","journal-title":"Parasitology"},{"issue":"1","key":"pntd.0011749.ref006","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.chom.2020.10.002","article-title":"Schistosoma mansoni eggs modulate the timing of granuloma formation to promote transmission.","volume":"29","author":"KK Takaki","year":"2021","journal-title":"Cell Host & Microbe."},{"issue":"3 & 4","key":"pntd.0011749.ref007","article-title":"On the Development, Length of Life and Death of the Eggs of Bilharzia jap\u00f3nica in the Tissues of the Host.","volume":"46","author":"H. Vogel","year":"1942","journal-title":"Deutsche Tropenmedizinische Zeitschrift."},{"key":"pntd.0011749.ref008","doi-asserted-by":"crossref","first-page":"857","DOI":"10.2307\/3281046","article-title":"Nutritional requirements of Schistosoma japonicum eggs","author":"M Kawanaka","year":"1983","journal-title":"The Journal of parasitology"},{"issue":"2","key":"pntd.0011749.ref009","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/bbrc.2001.5386","article-title":"Cholesteryl ester transfer protein deficiency causes slow egg embryonation of Schistosoma japonicum","volume":"286","author":"K Okumura-Noji","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pntd.0011749.ref010","doi-asserted-by":"crossref","first-page":"176","DOI":"10.7555\/JBR.29.20150005","article-title":"Prevention of fatal hepatic complication in schistosomiasis by inhibition of CETP","volume":"29","author":"S Yokoyama","year":"2015","journal-title":"Journal of Biomedical Research"},{"issue":"4","key":"pntd.0011749.ref011","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bbalip.2013.12.014","article-title":"A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum","volume":"1841","author":"S. Yokoyama","year":"2014","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids."},{"issue":"3","key":"pntd.0011749.ref012","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1096\/fj.12-219816","article-title":"CD36-related protein in Schistosoma japonicum: candidate mediator of selective cholesteryl ester uptake from high-density lipoprotein for egg maturation","volume":"27","author":"K Okumura-Noji","year":"2013","journal-title":"Faseb j"},{"key":"pntd.0011749.ref013","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.807289","article-title":"HDL Receptor in Schistosoma japonicum Mediating Egg Embryonation: Potential Molecular Basis for High Prevalence of Cholesteryl Ester Transfer Protein Deficiency in East Asia.","volume":"10","author":"S. Yokoyama","year":"2022","journal-title":"Frontiers in Cell and Developmental Biology"},{"issue":"4","key":"pntd.0011749.ref014","doi-asserted-by":"crossref","first-page":"265","DOI":"10.5650\/jos.ess16020","article-title":"Recent Advances in Analytical Methods on Lipoprotein Subclasses: Calculation of Particle Numbers from Lipid Levels by Gel Permeation HPLC Using \"Spherical Particle Model\".","volume":"65","author":"M Okazaki","year":"2016","journal-title":"Journal of oleo science"},{"issue":"12","key":"pntd.0011749.ref015","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1365-3024.2006.00921.x","article-title":"Immunomodulation of the hepatic egg granuloma in Schistosoma japonicum-infected pigs","volume":"28","author":"M Hurst","year":"2006","journal-title":"Parasite immunology"},{"issue":"2","key":"pntd.0011749.ref016","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/0014-4894(74)90035-6","article-title":"Schistosoma mansoni: antigenic secretions and the etiology of egg granulomas in mice","volume":"35","author":"LM Hang","year":"1974","journal-title":"Experimental parasitology"},{"issue":"7","key":"pntd.0011749.ref017","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.pt.2020.04.012","article-title":"Schistosomiasis control: leave no age group behind","volume":"36","author":"CL Faust","year":"2020","journal-title":"Trends in parasitology"},{"issue":"3","key":"pntd.0011749.ref018","doi-asserted-by":"crossref","first-page":"e0009189","DOI":"10.1371\/journal.pntd.0009189","article-title":"Efficacy of praziquantel has been maintained over four decades (from 1977 to 2018): A systematic review and meta-analysis of factors influence its efficacy.","volume":"15","author":"M Fukushige","year":"2021","journal-title":"PLoS Neglected Tropical Diseases"},{"issue":"8","key":"pntd.0011749.ref019","doi-asserted-by":"crossref","first-page":"e0008635","DOI":"10.1371\/journal.pntd.0008635","article-title":"Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment","volume":"14","author":"VHS Miranda","year":"2020","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"pntd.0011749.ref020","article-title":"The Role of Praziquantel in the Prevention and Treatment of Fibrosis Associated with Schistosomiasis: A Review.","volume":"2022","author":"X Niu","year":"2022","journal-title":"Journal of Tropical Medicine"},{"issue":"2","key":"pntd.0011749.ref021","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.pt.2018.10.005","article-title":"Advancing the Development of a Human Schistosomiasis Vaccine","volume":"35","author":"PJ Hotez","year":"2019","journal-title":"Trends in parasitology"},{"issue":"1","key":"pntd.0011749.ref022","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12929-020-0621-y","article-title":"Schistosomiasis vaccine development: update on human clinical trials","volume":"27","author":"AJ Molehin","year":"2020","journal-title":"Journal of biomedical science"},{"issue":"1","key":"pntd.0011749.ref023","doi-asserted-by":"crossref","DOI":"10.1111\/pim.12392","article-title":"Protective role of IL-22 against Schistosoma mansoni soluble egg antigen-induced granuloma in Vitro","volume":"39","author":"S Nady","year":"2017","journal-title":"Parasite immunology"},{"issue":"1","key":"pntd.0011749.ref024","doi-asserted-by":"crossref","first-page":"38","DOI":"10.24911\/IJMDC.2.1.7","article-title":"Anti-IL-17 markedly inhibited the in vitro granuloma induced by Schistosoma mansoni soluble egg antigen","volume":"2","author":"A Ezz","year":"2018","journal-title":"International Journal of Medicine in Developing Countries"},{"issue":"2","key":"pntd.0011749.ref025","first-page":"279","article-title":"The Schistosoma japonicum egg granuloma","volume":"80","author":"KS Warren","year":"1975","journal-title":"The American Journal of Pathology"},{"issue":"4","key":"pntd.0011749.ref026","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41577-019-0123-x","article-title":"Adaptive immune responses to primary and secondary dengue virus infections.","volume":"19","author":"AL St. John","year":"2019","journal-title":"Nature Reviews Immunology"},{"key":"pntd.0011749.ref027","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2307\/3283884","article-title":"Primary and secondary Toxoplasma gondii infection in normal and feline immunodeficiency virus-infected cats","author":"MR Lappin","year":"1996","journal-title":"The Journal of parasitology"},{"issue":"24","key":"pntd.0011749.ref028","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1056\/NEJMoa2026920","article-title":"Phase 1\u20132 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine","volume":"383","author":"C Keech","year":"2020","journal-title":"New England Journal of Medicine"},{"issue":"3","key":"pntd.0011749.ref029","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1084\/jem.121.3.323","article-title":"The catabolism of homologous and heterologous 7S gamma globulin fragments","volume":"121","author":"HL Spiegelberg","year":"1965","journal-title":"The Journal of Experimental Medicine"},{"issue":"8","key":"pntd.0011749.ref030","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/eji.1830130802","article-title":"Effect of protein A and its fragment B on the catabolic and Fc receptor sites of IgG","volume":"13","author":"S Dima","year":"1983","journal-title":"European journal of immunology"},{"issue":"1","key":"pntd.0011749.ref031","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.exppara.2011.07.018","article-title":"Schistosoma mansoni: the egg, biosynthesis of the shell and interaction with the host","volume":"132","author":"S deWalick","year":"2012","journal-title":"Experimental parasitology"},{"issue":"26","key":"pntd.0011749.ref032","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1056\/NEJM198106253042616","article-title":"Decreased serum HDL3, cholesterol levels in cirrhosis of the liver","volume":"304","author":"M Okazaki","year":"1981","journal-title":"The New England journal of medicine"},{"issue":"3","key":"pntd.0011749.ref033","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4269\/ajtmh.1994.50.281","article-title":"Kinetics of egg production and egg excretion by Schistosoma mansoni and S. japonicum in mice infected with a single pair of worms","volume":"50","author":"AW Cheever","year":"1994","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"6","key":"pntd.0011749.ref034","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","article-title":"Arunachalam P, O\u2019Hagan DT. Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"S. Pulendran B","year":"2021","journal-title":"Nature Reviews Drug Discovery"},{"issue":"9","key":"pntd.0011749.ref035","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41551-020-00650-4","article-title":"Transdermal microneedles for the programmable burst release of multiple vaccine payloads","volume":"5","author":"KT Tran","year":"2021","journal-title":"Nature Biomedical Engineering"},{"issue":"8","key":"pntd.0011749.ref036","doi-asserted-by":"crossref","first-page":"2001812","DOI":"10.1002\/adhm.202001812","article-title":"Next-generation vaccines: nanoparticle-mediated dna and mrna delivery","volume":"10","author":"W Ho","year":"2021","journal-title":"Advanced Healthcare Materials"},{"issue":"1","key":"pntd.0011749.ref037","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0166-6851(90)90100-Z","article-title":"Purification of a putative lipoprotein receptor from Schistosoma japonicum adult worms","volume":"41","author":"MV Rogers","year":"1990","journal-title":"Molecular and biochemical parasitology"},{"issue":"2","key":"pntd.0011749.ref038","first-page":"229","article-title":"Characterization of human low density lipoprotein binding proteins on the surface of schistosomula of Schistosoma mansoni","volume":"57","author":"X Xu","year":"1992","journal-title":"European journal of cell biology"},{"issue":"10","key":"pntd.0011749.ref039","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/S1357-2725(03)00105-5","article-title":"A Schistosoma japonicum very low-density lipoprotein-binding protein","volume":"35","author":"J Fan","year":"2003","journal-title":"The international journal of biochemistry & cell biology"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T18:26:52Z","timestamp":1701282412000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011749"}},"subtitle":[],"editor":[{"given":"Javier","family":"Sotillo","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0011749","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,29]]}}}