Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: A dose-finding trial in two centres

Benjamin Mordmüller, Christian Supan, Kim Lee Sim, Gloria P. Gómez-Pérez, Carmen Lucelly Ospina Salazar, Jana Held, Stefanie Bolte, Meral Esen, Serena Tschan, Fanny Joanny, Carlos Lamsfus Calle, Sascha J.Z. Löhr, Albert Lalremruata, Anusha Gunasekera, Eric R. James, Peter F. Billingsley, Adam Richman, Sumana Chakravarty, Almudena Legarda, Jose MuñozRosa M. Antonijoan, Maria Rosa Ballester, Stephen L. Hoffman, Pedro L. Alonso, Peter G. Kremsner

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© 2015 Mordmüller et al.; licensee BioMed Central. Background: Controlled human malaria infection (CHMI) accelerates development of anti-malarial interventions. So far, CHMI is done by exposure of volunteers to bites of five mosquitoes carrying Plasmodium falciparum sporozoites (PfSPZ), a technique available in only a few centres worldwide. Mosquito-mediated CHMI is logistically complex, exact PfSPZ dosage is impossible and live mosquito-based interventions are not suitable for further clinical development. Methods: An open-labelled, randomized, dose-finding study in 18-45 year old, healthy, malaria-naïve volunteers was performed to assess if intravenous (IV) injection of 50 to 3,200 aseptic, purified, cryopreserved PfSPZ is safe and achieves infection kinetics comparable to published data of mosquito-mediated CHMI. An independent study site verified the fully infectious dose using direct venous inoculation of PfSPZ. Parasite kinetics were assessed by thick blood smear microscopy and quantitative real time PCR. Results: IV inoculation with 50, 200, 800, or 3,200 PfSPZ led to parasitaemia in 1/3, 1/3, 7/9, and 9/9 volunteers, respectively. The geometric mean pre-patent period (GMPPP) was 11.2 days (range 10.5-12.5) in the 3,200 PfSPZ IV group. Subsequently, six volunteers received 3,200 PfSPZ by direct venous inoculation at an independent investigational site. All six developed parasitaemia (GMPPP: 11.4 days, range: 10.4-12.3). Inoculation of PfSPZ was safe. Infection rate and pre-patent period depended on dose, and injection of 3,200 PfSPZ led to a GMPPP similar to CHMI with five PfSPZ-infected mosquitoes. The infectious dose of PfSPZ predicted dosage of radiation-attenuated PfSPZ required for successful vaccination. Conclusions: IV inoculation of PfSPZ is safe, well tolerated and highly reproducible. It shall further accelerate development of anti-malarial interventions through standardization and facilitation of CHMI. Beyond this, rational dose selection for whole PfSPZ-based immunization and complex study designs are now possible. Trial registration: NCT01624961 and NCT01771848.
Original languageEnglish
Article number117
JournalMalaria Journal
Issue number1
Publication statusPublished - 1 Jan 2015


  • Clinical trial
  • Controlled human malaria infection
  • Malaria
  • Microbial challenge
  • Plasmodium falciparum sporozoite


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