{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:23:11Z","timestamp":1793254991050,"version":"4.5.0"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,22]]},"abstract":"<jats:p>\n                    Sporozoite-based approaches currently represent the most effective vaccine strategies for induction of sterile protection against\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (\n                    <jats:italic>Pf<\/jats:italic>\n                    ) malaria. Clinical development of subunit vaccines is almost exclusively centered on the circum-sporozoite protein (CSP), an abundantly expressed protein on the sporozoite membrane. Anti-CSP antibodies are able to block sporozoite invasion and development in human hepatocytes and subsequently prevent clinical malaria. Here, we have investigated whether sporozoite-induced human antibodies with specificities different from CSP can reduce\n                    <jats:italic>Pf-<\/jats:italic>\n                    liver stage development. IgG preparations were obtained from 12 volunteers inoculated with a protective immunization regime of whole sporozoites under chloroquine prophylaxis. These IgGs were depleted for CSP specificity by affinity chromatography. Recovered non-CSP antibodies were tested for sporozoite membrane binding and for functional inhibition of sporozoite invasion of a human hepatoma cell line and hepatocytes both in vitro and in vivo. Postimmunization IgGs depleted for CS specificity of 9 of 12 donors recognized sporozoite surface antigens. Samples from 5 of 12 donors functionally reduced parasite-liver cell invasion or development using the hepatoma cell line HC-04 and FRG-huHep mice containing human liver cells. The combined data provide clear evidence that non-CSP proteins, as yet undefined, do represent antibody targets for functional immunity against\n                    <jats:italic>Pf<\/jats:italic>\n                    parasites responsible for malaria.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.153524","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T12:15:15Z","timestamp":1644927315000},"source":"Crossref","is-referenced-by-count":10,"title":["Human antibodies against noncircumsporozoite proteins block Plasmodium falciparum parasite development in hepatocytes"],"prefix":"10.1172","volume":"7","author":[{"given":"Amanda","family":"Fabra-Garc\u00eda","sequence":"first","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7279-6058","authenticated-orcid":true,"given":"Annie S.P.","family":"Yang","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije C.","family":"Behet","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zen","family":"Yap","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youri","family":"van Waardenburg","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarnendu","family":"Kaviraj","sequence":"additional","affiliation":[{"name":"Gennova Biopharmaceuticals Ltd., Pune, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjerstin","family":"Lanke","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert-Jan","family":"van Gemert","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0686-370X","authenticated-orcid":true,"given":"Matthijs M.","family":"Jore","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-094X","authenticated-orcid":true,"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Sauerwein","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"B1","unstructured":"WHO. World Malaria Report 2020. https:\/\/www.who.int\/publications\/i\/item\/9789240015791 Accessed February 15, 2022"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.4363-4369.2005"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000399"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.08.010"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00861.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90093-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005606"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60721-8"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00943-0"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4513"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.007"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.08.014"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034031"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0228-6"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01227"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0923-4"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805832"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature21060"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-136"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-017-0028-2"},{"issue":"1","key":"B21","doi-asserted-by":"crossref","DOI":"10.1128\/mSphereDirect.00027-19","article-title":"Antibody biomarkers associated with sterile protection induced by controlled human malaria infection under chloroquine prophylaxis","volume":"4","author":"Obiero","year":"2019","journal-title":"mSphere"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/srep03549"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12608"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu354"},{"key":"B25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/978-1-4939-6506-9_8","article-title":"Successful engraftment of human hepatocytes in uPA-SCID and FRG\u00ae KO mice","volume":"1506","author":"Foquet","year":"2017","journal-title":"Methods Mol Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.7.1597"},{"issue":"9","key":"B27","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12745","article-title":"AMA1 and MAEBL are important for Plasmodium falciparum sporozoite infection of the liver","volume":"19","author":"Yang","year":"2017","journal-title":"Cell Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.05024.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3604-3608.2004"},{"issue":"2","key":"B30","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00498-16","article-title":"The Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites as a candidate for preerythrocytic and transmission-blocking vaccines","volume":"85","author":"Espinosa","year":"2017","journal-title":"Infect Immun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.3.1230"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01415-09"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.117"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abg2344"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-326"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(82)90116-X"},{"key":"B37","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1017\/S0031182000062065","article-title":"Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes","volume":"98 Pt 2","author":"Ponnudurai","year":"1989","journal-title":"Parasitology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2915.1989.tb00473.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01108-12"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay2578"},{"issue":"7","key":"B41","doi-asserted-by":"crossref","first-page":"e00920","DOI":"10.1128\/IAI.00920-17","article-title":"The complement system contributes to functional antibody-mediated responses induced by immunization with Plasmodium falciparum malaria sporozoites","volume":"86","author":"Behet","year":"2018","journal-title":"Infect Immun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4512"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(91)90012-N"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-421"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1997.2637"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-430"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/153524\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:36:31Z","timestamp":1779147391000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/153524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3,22]]},"published-print":{"date-parts":[[2022,3,22]]}},"alternative-id":["10.1172\/jci.insight.153524"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.153524","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]},"article-number":"e153524"}}