title: Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis: A Randomized Controlled Trial.
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.
authors.forename: Guido J H
authors.initials: GJH
authors.lastname: Bastiaens
authors.forename: Maurits P A
authors.initials: MPA
authors.lastname: van Meer
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Obiero
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Vatanshenassan
authors.forename: Tim
authors.initials: T
authors.lastname: van Grinsven
authors.forename: B Kim Lee
authors.initials: BKL
authors.lastname: Sim
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.forename: Else M
authors.initials: EM
authors.lastname: Bijker
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Wouter
authors.initials: W
authors.lastname: Graumans
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.forename: André J A M
authors.initials: AJAM
authors.lastname: van der Ven
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology / Q000502:physiology; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D015925:Cryopreservation; D004311:Double-Blind Method; D006801:Humans; D007114:Immunization; D007271:Injections, Intradermal; D007299:Insect Bites and Stings; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D061214:Patient Safety; D010963:Plasmodium falciparum / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine