{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:46:03Z","timestamp":1781909163261,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24790399, 26860276, 18H06139"],"award-info":[{"award-number":["24790399, 26860276, 18H06139"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Human malaria vaccine trials have revealed vaccine efficacy but improvement is still needed. In this study, we aimed to re-evaluate vaccination with blood-stage naturally attenuated parasites, as a whole-organism vaccine model against cross-strain and cross-species malaria, to establish a better vaccination strategy. C57BL\/6 mice controlled blood-stage Plasmodium yoelii 17XNL (PyNL) within 1 month of infection, while mice with a variety of immunodeficiencies demonstrated different susceptibilities to PyNL, including succumbing to hyperparasitemia. However, after recovery, survivors had complete protection against a challenge with the lethal strain PyL. Unlike cross-strain protection, PyNL-recovered mice failed to induce sterile immunity against Plasmodium berghei ANKA, although prolonged survival was observed in some vaccinated mice. Splenomegaly is a typical characteristic of malaria; the splenic structure became reorganized to prioritize extra-medullary hematopoiesis and to eliminate parasites. We also found that the peritoneal lymph node was enlarged, containing activated\/memory phenotype cells that did not confer protection against PyL challenge. Hemozoins remained in the spleen several months after PyNL infection. Generation of an attenuated human blood-stage parasite expressing proteins from multiple species of malaria would greatly improve anti-malaria vaccination.<\/jats:p>","DOI":"10.3390\/vaccines8030375","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T04:46:01Z","timestamp":1594701961000},"page":"375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Potential and Limitations of Cross-Protective Vaccine against Malaria by Blood-Stage Naturally Attenuated Parasite"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9049-8102","authenticated-orcid":false,"given":"Takashi","family":"Imai","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan"},{"name":"Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutomo","family":"Suzue","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha","family":"Ngo-Thanh","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-5344","authenticated-orcid":false,"given":"Chikako","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"Department of Parasitology, National Institute of Infectious Diseases, Tokyo 162-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Hisaeda","sequence":"additional","affiliation":[{"name":"Department of Parasitology, National Institute of Infectious Diseases, Tokyo 162-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.cll.2009.10.001","article-title":"Malaria","volume":"30","author":"Garcia","year":"2010","journal-title":"Clin. 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