{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T01:23:14Z","timestamp":1769044994075,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI001170-05"],"award-info":[{"award-number":["AI001170-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs, such as primaquine, act against liver-stage parasites. Here, we evaluated CVac regimens using primaquine and\/or chloroquine as the partner drug to discern whether blood-stage parasite exposure impacts protection against homologous controlled human malaria infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In a Phase I, randomized, partial double-blind, placebo-controlled study of 36 malaria-naive adults, all CVac subjects received chloroquine prophylaxis and bites from 12\u201315 P. falciparum\u2013infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received postexposure primaquine (CVac-primaquine\/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After a chloroquine washout, subjects, including treatment-naive infectivity controls, underwent homologous, PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>No serious adverse events occurred. During CVac, all but 1 subject in the study remained blood-smear negative, while only 1 subject (primaquine\/chloroquine arm) remained polymerase chain reaction\u2013negative. Upon challenge, compared to infectivity controls, 3\/3 chloroquine arm subjects displayed delayed patent parasitemia (P = .01) but not sterile protection, while 3\/11 primaquine\/chloroquine subjects remained blood-smear negative.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CVac-primaquine\/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine postexposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT01500980.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz1010","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T19:29:57Z","timestamp":1570822197000},"page":"1481-1490","source":"Crossref","is-referenced-by-count":10,"title":["Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults"],"prefix":"10.1093","volume":"71","author":[{"given":"Sara A","family":"Healy","sequence":"first","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Washington, Seattle, Washington, USA"},{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean C","family":"Murphy","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Department of Laboratory Medicine and Microbiology, University of Washington, Seattle, Washington, USA"},{"name":"Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen C C","family":"Hume","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Shelton","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley C","family":"Van Voorhis","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe","family":"Moodie","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Metch","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruobing","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Silver-Brace","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Fishbaugher","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia C","family":"Finney","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richa","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean R","family":"Marcsisin","sequence":"additional","affiliation":[{"name":"Military Malaria Research Program, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte V","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Warner-Lubin","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"C3 Research Associates, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela K","family":"Talley","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Wong-Madden","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Stuart","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Wald","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Microbiology, University of Washington, Seattle, Washington, USA"},{"name":"Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"},{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA"},{"name":"Department of Epidemiology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan H","family":"Kappe","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G","family":"Kublin","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick E","family":"Duffy","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Seattle, Washington, USA"},{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 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