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The SPZ\u2019s main surface antigen, the circumsporozoite protein (CSP), plays a pivotal role in SPZ biology and constitutes the immunodominant target for host antibodies. In this study, we raised single-domain antibodies (sdAbs) against CSP from\n P. falciparum<\/jats:italic>\n (PfCSP) by immunizing two alpacas with recombinant versions of the antigen. We found that all identified sdAbs specifically target PfCSP\u2019s globular\n \n \n \n \n \n \u03b1<\/mml:mi>\n <\/mml:mstyle>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n TSR domain without cross-reacting with\n P. berghei<\/jats:italic>\n CSP. Further characterization revealed that most sdAbs recognize native PfCSP on the SPZ surface, although they do not have any inhibitory effect on hepatocyte binding and invasion. Structural studies showed that all binders target the previously identified\n \n \n \n \n \n \u03b1<\/mml:mi>\n <\/mml:mstyle>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n -epitope, confirming the non-protective nature of this epitope. Comparison of sdAb binding to midgut and salivary gland SPZs revealed a shift in the exposure and accessibility of the\n \n \n \n \n \n \u03b1<\/mml:mi>\n <\/mml:mstyle>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n -epitope. Hence, our findings provide further evidence that CSP undergoes structural changes during SPZ development in the mosquito host.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/iai.00081-25","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T09:00:24Z","timestamp":1745830824000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Evidence for a model of conformational change by the\n Plasmodium falciparum<\/i>\n circumsporozoite protein during sporozoite development in the mosquito host through the use of camelid single-domain antibodies"],"prefix":"10.1128","volume":"93","author":[{"given":"Rob","family":"Geens","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008x57b05","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, Department of Pharmaceutical Sciences, University of Antwerp","place":["Antwerp, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"De Vocht","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008x57b05","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, Department of Pharmaceutical Sciences, University of Antwerp","place":["Antwerp, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela C.","family":"Aguirre-Botero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection & Immunity","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Vincke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006e5kg04","id-type":"ROR","asserted-by":"publisher"}],"name":"Lab of Cellular and Molecular Immunology (CMIM), Brussels Center for Immunology (BCIM), Department of Bioengineering Sciences, Vrije Universiteit Brussel","place":["Brussels, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/04q4ydz28","id-type":"ROR","asserted-by":"publisher"}],"name":"Myeloid Cell Immunology Lab, VIB Center for Inflammation Research","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ema","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006e5kg04","id-type":"ROR","asserted-by":"publisher"}],"name":"Lab of Cellular and Molecular Immunology (CMIM), Brussels Center for Immunology (BCIM), Department of Bioengineering Sciences, Vrije Universiteit Brussel","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Magez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006e5kg04","id-type":"ROR","asserted-by":"publisher"}],"name":"Lab of Cellular and Molecular Immunology (CMIM), Brussels Center for Immunology (BCIM), Department of Bioengineering Sciences, Vrije Universiteit Brussel","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Muyldermans","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006e5kg04","id-type":"ROR","asserted-by":"publisher"}],"name":"Lab of Cellular and Molecular Immunology (CMIM), Brussels Center for Immunology (BCIM), Department of Bioengineering Sciences, Vrije Universiteit Brussel","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogerio","family":"Amino","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0495fxg12","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection & Immunity","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-0983","authenticated-orcid":false,"given":"Yann G.-J.","family":"Sterckx","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008x57b05","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, Department of Pharmaceutical Sciences, University of Antwerp","place":["Antwerp, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO. 2024. 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