{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:22:01Z","timestamp":1774506121772,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,23]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,23]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  An effective vaccine capable of inducing sterile protection against\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  , the causative agent of malaria, is critical to aid global eradication. Whole-organism vaccines using liver-infective sporozoites provide high levels of sterile protection against pre-erythrocytic infection. Yet, determinants of sporozoite immunogenicity remain poorly characterized. Using rodent models of vaccination, we demonstrate that the ability of\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  sporozoites to actively migrate through multiple host cells prior to infecting hepatocytes is required for sterilizing immunity, regardless of the time of intrahepatic development of immunizing parasites. We further establish that host cell traversal is sufficient to trigger robust protection against\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  hepatic infection. Impaired cell traversal precludes protective liver-resident memory CD8 T cell responses following vaccination, but not the production of anti-plasmodial antibodies. Our findings challenge the prevailing notion that intrahepatic parasite development is the sole determinant of whole-sporozoite vaccination-induced protection, and highlight parasite behavior traits as critical immunogenic events shaping sterilizing cellular immunity against\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  liver stages.\n                <\/jats:p>","DOI":"10.64898\/2026.03.20.713177","type":"posted-content","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:45:25Z","timestamp":1774323925000},"source":"Crossref","is-referenced-by-count":0,"title":["Host cell traversal by\n                  <i>Plasmodium<\/i>\n                  parasites is essential for sterilizing hepatic cellular immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-6644","authenticated-orcid":false,"given":"Ana","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-5325","authenticated-orcid":false,"given":"Ant\u00f3nio M.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Current affiliation: SGS Portugal S.A., Rua Cesina Ad\u00e3es Bermudes Lote 11 N\u00b0 1, 1600-604 Lisboa, Portugal"}]},{"given":"Rute","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-2879","authenticated-orcid":false,"given":"Helena","family":"Nunes-Caba\u00e7o","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-1529","authenticated-orcid":false,"given":"Sofia","family":"Marques","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-2521","authenticated-orcid":false,"given":"Nuno","family":"Valente-Leal","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6746-932X","authenticated-orcid":false,"given":"Cristina","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-9562","authenticated-orcid":false,"given":"Marc","family":"Veldhoen","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1746-6029","authenticated-orcid":false,"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-1041","authenticated-orcid":false,"given":"Maria M.","family":"Mota","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-7196","authenticated-orcid":false,"given":"\u00c2ngelo Ferreira","family":"Chora","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, 1649-028, Lisbon, Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisbon, Portugal"}]}],"member":"54368","reference":[{"key":"2026032521150343000_2026.03.20.713177v1.1","unstructured":"World Health Organization. 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