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Whole\u2010sporozoite (Wsp) vaccines, which induce efficient immune responses against the pre\u2010erythrocytic (PE) stages (sporozoites and liver forms) of <jats:italic>Plasmodium<\/jats:italic> parasites, the causative agents of malaria, are among the most promising immunization strategies tested until present. Several Wsp PE vaccination approaches are currently under evaluation in the clinic, including radiation\u2010 or genetically\u2010attenuated <jats:italic>Plasmodium<\/jats:italic> sporozoites, live parasites combined with chemoprophylaxis, or genetically modified rodent <jats:italic>Plasmodium<\/jats:italic> parasites. In addition to the assessment of their protective efficacy, clinical trials of Wsp PE vaccine candidates inevitably involve the thorough investigation of the immune responses elicited by vaccination, as well as the identification of correlates of protection. Here, we review the main methodologies employed to dissect the humoral and cellular immune responses observed in the context of Wsp PE vaccine clinical trials and discuss future strategies to further deepen the knowledge generated by these studies, providing a toolbox for the in\u2010depth analysis of vaccine\u2010induced immunogenicity.<\/jats:p>","DOI":"10.1111\/febs.16016","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T07:26:12Z","timestamp":1621149972000},"page":"3335-3359","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A guide to investigating immune responses elicited by whole\u2010sporozoite pre\u2010erythrocytic vaccines against malaria"],"prefix":"10.1111","volume":"289","author":[{"given":"Diana","family":"Moita","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Faculdade de Medicina Universidade de Lisboa  Portugal"}]},{"given":"Helena","family":"Nunes\u2010Caba\u00e7o","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Faculdade de Medicina Universidade de Lisboa  Portugal"}]},{"given":"Ant\u00f3nio M.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Faculdade de Medicina Universidade de Lisboa  Portugal"}]},{"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes Faculdade de Medicina Universidade de Lisboa  Portugal"}]}],"member":"311","published-online":{"date-parts":[[2021,6]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization(2020).World Malaria Report 2020.https:\/\/www.who.int\/publications\/i\/item\/9789240015791"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15535"},{"key":"e_1_2_11_4_1","first-page":"1","article-title":"Are malaria elimination efforts on right track? 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