학술논문
Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis: A Randomized Controlled Trial
Document Type
article
Author
Bastiaens, Guido JH; van Meer, Maurits PA; Scholzen, Anja; Obiero, Joshua M; Vatanshenassan, Mansoureh; van Grinsven, Tim; Sim, B Kim Lee; Billingsley, Peter F; James, Eric R; Gunasekera, Anusha; Bijker, Else M; van Gemert, Geert-Jan; van de Vegte-Bolmer, Marga; Graumans, Wouter; Hermsen, Cornelus C; de Mast, Quirijn; van der Ven, André JAM; Hoffman, Stephen L; Sauerwein, Robert W
Source
American Journal of Tropical Medicine and Hygiene. 94(3)
Subject
Language
Abstract
Immunization of volunteers under chloroquine prophylaxis by bites of Plasmodium falciparum sporozoite (PfSPZ)-infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3× monthly immunizations with 7.5 × 10(4) PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60 days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2) became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR. Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up to 3 × 10(5) PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf CHMI.