title: Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites.
abstract: Controlled human malaria infection with sporozoites is a standardized and powerful tool for evaluation of malaria vaccine and drug efficacy but so far only applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes. We assessed in an open label Phase 1 trial, infection after intradermal injection of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers. Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of 6 volunteers in each group. There were no differences between groups in time until parasitemia by microscopy or quantitative polymerase chain reaction, parasite kinetics, clinical symptoms, or laboratory values. This is the first successful infection by needle and syringe with PfSPZ manufactured in compliance with regulatory standards. After further optimization, the use of such PfSPZ may facilitate and accelerate clinical development of novel malaria drugs and vaccines.
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.forename: Else M
authors.initials: EM
authors.lastname: Bijker
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: Guido J H
authors.initials: GJH
authors.lastname: Bastiaens
authors.forename: Anne C
authors.initials: AC
authors.lastname: Teirlinck
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.forename: Theo
authors.initials: T
authors.lastname: Arens
authors.forename: André J A M
authors.initials: AJAM
authors.lastname: van der Ven
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Velmurugan
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D006801:Humans; D016778:Malaria, Falciparum / Q000628:therapy*; D010963:Plasmodium falciparum / Q000254:growth & development*; D016133:Polymerase Chain Reaction; D034101:Sporozoites