{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:48:39Z","timestamp":1792889319642,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009594","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272201300019I"],"award-info":[{"award-number":["HHSN272201300019I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["2R44AI058375-11"],"award-info":[{"award-number":["2R44AI058375-11"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    PfSPZ-CVac combines \u2018PfSPZ Challenge\u2019, which consists of infectious\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    sporozoites (PfSPZ), with concurrent antimalarial chemoprophylaxis. In a previously-published PfSPZ-CVac study, three doses of 5.12x10\n                    <jats:sup>4<\/jats:sup>\n                    PfSPZ-CVac given 28 days apart had 100% vaccine efficacy (VE) against controlled human malaria infection (CHMI) 10 weeks after the last immunization, while the same dose given as three injections five days apart had 63% VE. Here, we conducted a dose escalation trial of similarly condensed schedules. Of the groups proceeding to CHMI, the first study group received three direct venous inoculations (DVIs) of a dose of 5.12x10\n                    <jats:sup>4<\/jats:sup>\n                    PfSPZ-CVac seven days apart and the next full dose group received three DVIs of a higher dose of 1.024x10\n                    <jats:sup>5<\/jats:sup>\n                    PfSPZ-CVac five days apart. CHMI (3.2x10\n                    <jats:sup>3<\/jats:sup>\n                    PfSPZ Challenge) was performed by DVI 10 weeks after the last vaccination. In both CHMI groups, transient parasitemia occurred starting seven days after each vaccination. For the seven-day interval group, the second and third vaccinations were therefore administered coincident with parasitemia from the prior vaccination. Parasitemia was associated with systemic symptoms which were severe in 25% of subjects. VE in the seven-day group was 0% (7\/7 infected) and in the higher-dose, five-day group was 75% (2\/8 infected). Thus, the same dose of PfSPZ-CVac previously associated with 63% VE when given on a five-day schedule in the prior study had zero VE here when given on a seven-day schedule, while a double dose given on a five-day schedule here achieved 75% VE. The relative contributions of the five-day schedule and\/or the higher dose to improved VE warrant further investigation. It is notable that administration of PfSPZ-CVac on a schedule where vaccine administration coincided with blood-stage parasitemia was associated with an absence of sterile protective immunity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trials registration<\/jats:bold>\n                    :\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02773979\" xlink:type=\"simple\">NCT02773979<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009594","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T15:57:42Z","timestamp":1622217462000},"page":"e1009594","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":59,"title":["PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-0131","authenticated-orcid":true,"given":"Sean C.","family":"Murphy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-4541","authenticated-orcid":true,"given":"Gregory A.","family":"Deye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Kim Lee","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Galbiati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0557-5789","authenticated-orcid":true,"given":"Jessie K.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-9941","authenticated-orcid":true,"given":"Kristen 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