{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:39:10Z","timestamp":1774877950627,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-007155"],"award-info":[{"award-number":["INV-007155"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>In addition to vector control, long-lasting insecticidal nets and case management, the prevention of infection through vaccination and\/or chemoprevention are playing an increasing role in the drive to eradicate malaria. These preventative approaches represent opportunities for improvement: new drugs may be discovered that target the early infectious stages of the Plasmodium parasite in the liver (rather than the symptomatic, abundant blood stage), and new, exciting vaccination technologies have recently been validated (using mRNA or novel adjuvants). Exploiting these possibilities requires the availability of humanized mouse models that support P. falciparum infection yet avoid the hazardous use of infectious mosquitoes. Here, we show that commercially available P. falciparum sporozoites and FRG mice carrying human hepatocytes and red blood cells faithfully recapitulate the early human malaria disease process, presenting an opportunity to use this model for the evaluation of prophylactic treatments with a novel mode of action.<\/jats:p>","DOI":"10.3390\/microorganisms11092209","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T11:33:25Z","timestamp":1693481605000},"page":"2209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Using Cryopreserved Plasmodium falciparum Sporozoites in a Humanized Mouse Model to Study Early Malaria Infection Processes and Test Prophylactic Treatments"],"prefix":"10.3390","volume":"11","author":[{"given":"Mar\u00eda-Bel\u00e9n","family":"Jim\u00e9nez-D\u00edaz","sequence":"first","affiliation":[{"name":"The Art of Discovery, 48160 Derio, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0769-9649","authenticated-orcid":false,"given":"J\u00f6rg J.","family":"M\u00f6hrle","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-8132","authenticated-orcid":false,"given":"I\u00f1igo","family":"Angulo-Barturen","sequence":"additional","affiliation":[{"name":"The Art of Discovery, 48160 Derio, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-2962","authenticated-orcid":false,"given":"Claudia","family":"Demarta-Gatsi","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, 1215 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). World Malaria Report 2022, World Health Organisation."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S2352-4642(22)00007-4","article-title":"Redoubling Efforts to Sustain Seasonal Malaria Chemoprevention","volume":"6","author":"Uhomoibhi","year":"2022","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Baral, R., Levin, A., Odero, C., Pecenka, C., Tabu, C., Mwendo, E., Bonsu, G., Bawa, J., Dadzie, J.F., and Charo, J. (2021). Costs of Continuing RTS,S\/ASO1E Malaria Vaccination in the Three Malaria Vaccine Pilot Implementation Countries. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250863"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(21)00943-0","article-title":"Efficacy of a Low-Dose Candidate Malaria Vaccine, R21 in Adjuvant Matrix-M, with Seasonal Administration to Children in Burkina Faso: A Randomised Controlled Trial","volume":"397","author":"Datoo","year":"2021","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.2353\/ajpath.2010.090691","article-title":"Murine Cerebral Malaria Is Associated with a Vasospasm-like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine","volume":"176","author":"Cabrales","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.coi.2009.05.015","article-title":"Immune Evasion by Malaria Parasites: A Challenge for Vaccine Development","volume":"21","author":"Casares","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/cmi.12277","article-title":"Of Men in Mice: The Success and Promise of Humanized Mouse Models for Human Malaria Parasite Infections","volume":"16","author":"Kaushansky","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.2217\/imt-2021-0102","article-title":"Plasmodium falciparum-Infected Humanized Mice: A Viable Preclinical Tool","volume":"13","author":"Tyagi","year":"2021","journal-title":"Immunotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/nbt1326","article-title":"Robust Expansion of Human Hepatocytes in Fah\u2212\/\u2212\/Rag2\u2212\/\u2212\/Il2rg\u2212\/\u2212 Mice","volume":"25","author":"Azuma","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2217\/fmb.12.27","article-title":"Development of Humanized Mouse Models to Study Human Malaria Parasite Infection","volume":"7","author":"Vaughan","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3389\/fimmu.2018.00524","article-title":"Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In Vivo","volume":"9","author":"Foquet","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101381","DOI":"10.1016\/j.isci.2020.101381","article-title":"A Humanized Mouse Model for Plasmodium vivax to Test Interventions That Block Liver Stage to Blood Stage Transition and Blood Stage Infection","volume":"23","author":"Roobsoong","year":"2020","journal-title":"iScience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0014-4894(55)90036-9","article-title":"Preservation of Viable Human Malaria Sporozoites by Low-Temperature Freezing","volume":"4","author":"Jeffery","year":"1955","journal-title":"Exp. Parasitol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.parint.2015.12.003","article-title":"A Simple and Efficient Method for Cryopreservation and Recovery of Viable Plasmodium vivax and P. falciparum Sporozoites","volume":"65","author":"Singh","year":"2016","journal-title":"Parasitol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Singh, N., Barnes, S.J., Kennedy, S., and Adams, J.H. (2017). Experimental Evaluation of Cryopreservative Solutions to Maintain in Vitro and in Vivo Infectivity of P. berghei Sporozoites. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177304"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1172\/JCI62684","article-title":"Complete Plasmodium falciparum Liver-Stage Development in Liver-Chimeric Mice","volume":"122","author":"Vaughan","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_17","first-page":"225","article-title":"Quantitative Measurement of Plasmodium-Infected Erythrocytes in Murine Models of Malaria by Flow Cytometry Using Bidimensional Assessment of SYTO-16 Fluorescence","volume":"75","author":"Mulet","year":"2009","journal-title":"Cytom. Part A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4269\/ajtmh.2012.12-0613","article-title":"Controlled Human Malaria Infections by Intradermal Injection of Cryopreserved Plasmodium falciparum Sporozoites","volume":"88","author":"Roestenberg","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/1475-2875-13-386","article-title":"Humanized HLA-DR4.RagKO.IL2R\u03b3cKO.NOD (DRAG) Mice Sustain the Complex Vertebrate Life Cycle of Plasmodium falciparum Malaria","volume":"13","author":"Wijayalath","year":"2014","journal-title":"Malar. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sheehy, S.H., Spencer, A.J., Douglas, A.D., Sim, B.K.L., Longley, R.J., Edwards, N.J., Poulton, I.D., Kimani, D., Williams, A.R., and Anagnostou, N.A. (2013). Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. 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