{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:47:52Z","timestamp":1790401672164,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T00:00:00Z","timestamp":1599955200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-15-C-0073"],"award-info":[{"award-number":["W81XWH-15-C-0073"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A live-attenuated Plasmodium falciparum sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same P. falciparum strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different P. falciparum strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy (VE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We immunized 4 groups that each contained 15 healthy, malaria-naive adults. Group 1 received 5 doses of 4.5 x 105 PfSPZ (Days 1, 3, 5, and 7; Week 16). Groups 2, 3, and 4 received 3 doses (Weeks 0, 8, and 16), with Group 2 receiving 9.0 \u00d7 105\/doses; Group 3 receiving 18.0 \u00d7 105\/doses; and Group 4 receiving 27.0 \u00d7 105 for dose 1 and 9.0 \u00d7 105 for doses 2 and 3. VE was assessed by heterologous CHMI after 12 or 24 weeks. Volunteers not protected at 12 weeks were boosted prior to repeat CHMI at 24 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 12-week CHMI, 6\/15 (40%) participants in Group 1 (P = .04) and 3\/15 (20%) participants in Group 2 remained aparasitemic, as compared to 0\/8 controls. At 24-week CHMI, 3\/13 (23%) participants in Group 3 and 3\/14 (21%) participants in Group 4 remained aparasitemic, versus 0\/8 controls (Groups 2\u20134, VE not significant). Postboost, 9\/14 (64%) participants versus 0\/8 controls remained aparasitemic (3\/6 in Group 1, P = .025; 6\/8 in Group 2, P = .002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Administering 4 stacked priming injections (multi-dose priming) resulted in 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single-dose priming was not significantly protective. Boosting unprotected subjects improved VE at 24 weeks, to 64%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trials Registration<\/jats:title><jats:p>NCT02601716.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciaa1294","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T19:12:29Z","timestamp":1599765149000},"page":"e2424-e2435","source":"Crossref","is-referenced-by-count":27,"title":["Multidose Priming and Delayed Boosting Improve<i>Plasmodium falciparum<\/i>Sporozoite Vaccine Efficacy Against Heterologous<i>P. falciparum<\/i>Controlled Human Malaria Infection"],"prefix":"10.1093","volume":"73","author":[{"given":"Kirsten E","family":"Lyke","sequence":"first","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Singer","sequence":"additional","affiliation":[{"name":"Naval Medical Research Center Malaria Department, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A","family":"Berry","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharina","family":"Reyes","sequence":"additional","affiliation":[{"name":"Naval Medical Research Center Malaria Department, Silver Spring, Maryland, USA"},{"name":"Henry M. 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