Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection

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 CH...

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Autores: Mordmüller, Benjamin, Supan, Christian, Sim, Kim Lee, Gómez-Pérez, Gloria P., Ospina Salazar, Carmen Lucelly, Held, Jana, Bolte, Stefanie, Esen, Meral, Tschan, Serena, Joanny, Fanny, Lamsfus Calle, Carlos, Löhr, Sascha J. Z., Lalremruata, Albert, Gunasekera, Anusha, James, Eric R., Billingsley, Peter F., Richman, Adam, Chakravarty, Sumana, Legarda, Almudena|||0000-0001-5088-6872, Muñoz Gutiérrez, José|||0000-0002-0945-1735, Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125, Ballester, Maria Rosa|||0000-0002-0472-9558, Hoffman, Stephen L., Alonso, Pedro L., Kremsner, Peter G.
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:254352
Acceso en línea:https://ddd.uab.cat/record/254352
https://dx.doi.org/urn:doi:10.1186/s12936-015-0628-0
Access Level:acceso abierto
Palabra clave:Malaria
Plasmodium falciparum sporozoite
Microbial challenge
Controlled human malaria infection
Clinical trial
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spelling Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infectiona dose-finding trial in two centresMordmüller, BenjaminSupan, ChristianSim, Kim LeeGómez-Pérez, Gloria P.Ospina Salazar, Carmen LucellyHeld, JanaBolte, StefanieEsen, MeralTschan, SerenaJoanny, FannyLamsfus Calle, CarlosLöhr, Sascha J. Z.Lalremruata, AlbertGunasekera, AnushaJames, Eric R.Billingsley, Peter F.Richman, AdamChakravarty, SumanaLegarda, Almudena|||0000-0001-5088-6872Muñoz Gutiérrez, José|||0000-0002-0945-1735Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125Ballester, Maria Rosa|||0000-0002-0472-9558Hoffman, Stephen L.Alonso, Pedro L.Kremsner, Peter G.MalariaPlasmodium falciparum sporozoiteMicrobial challengeControlled human malaria infectionClinical trialControlled 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. 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. 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. 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. ClinicalTrials.gov and .Universitat Autònoma de Barcelona 22015-01-0120152015-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/254352https://dx.doi.org/urn:doi:10.1186/s12936-015-0628-0reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2543522026-06-06T12:50:31Z
dc.title.none.fl_str_mv Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
a dose-finding trial in two centres
title Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
spellingShingle Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
Mordmüller, Benjamin
Malaria
Plasmodium falciparum sporozoite
Microbial challenge
Controlled human malaria infection
Clinical trial
title_short Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
title_full Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
title_fullStr Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
title_full_unstemmed Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
title_sort Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection
dc.creator.none.fl_str_mv Mordmüller, Benjamin
Supan, Christian
Sim, Kim Lee
Gómez-Pérez, Gloria P.
Ospina Salazar, Carmen Lucelly
Held, Jana
Bolte, Stefanie
Esen, Meral
Tschan, Serena
Joanny, Fanny
Lamsfus Calle, Carlos
Löhr, Sascha J. Z.
Lalremruata, Albert
Gunasekera, Anusha
James, Eric R.
Billingsley, Peter F.
Richman, Adam
Chakravarty, Sumana
Legarda, Almudena|||0000-0001-5088-6872
Muñoz Gutiérrez, José|||0000-0002-0945-1735
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Ballester, Maria Rosa|||0000-0002-0472-9558
Hoffman, Stephen L.
Alonso, Pedro L.
Kremsner, Peter G.
author Mordmüller, Benjamin
author_facet Mordmüller, Benjamin
Supan, Christian
Sim, Kim Lee
Gómez-Pérez, Gloria P.
Ospina Salazar, Carmen Lucelly
Held, Jana
Bolte, Stefanie
Esen, Meral
Tschan, Serena
Joanny, Fanny
Lamsfus Calle, Carlos
Löhr, Sascha J. Z.
Lalremruata, Albert
Gunasekera, Anusha
James, Eric R.
Billingsley, Peter F.
Richman, Adam
Chakravarty, Sumana
Legarda, Almudena|||0000-0001-5088-6872
Muñoz Gutiérrez, José|||0000-0002-0945-1735
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Ballester, Maria Rosa|||0000-0002-0472-9558
Hoffman, Stephen L.
Alonso, Pedro L.
Kremsner, Peter G.
author_role author
author2 Supan, Christian
Sim, Kim Lee
Gómez-Pérez, Gloria P.
Ospina Salazar, Carmen Lucelly
Held, Jana
Bolte, Stefanie
Esen, Meral
Tschan, Serena
Joanny, Fanny
Lamsfus Calle, Carlos
Löhr, Sascha J. Z.
Lalremruata, Albert
Gunasekera, Anusha
James, Eric R.
Billingsley, Peter F.
Richman, Adam
Chakravarty, Sumana
Legarda, Almudena|||0000-0001-5088-6872
Muñoz Gutiérrez, José|||0000-0002-0945-1735
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Ballester, Maria Rosa|||0000-0002-0472-9558
Hoffman, Stephen L.
Alonso, Pedro L.
Kremsner, Peter G.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Malaria
Plasmodium falciparum sporozoite
Microbial challenge
Controlled human malaria infection
Clinical trial
topic Malaria
Plasmodium falciparum sporozoite
Microbial challenge
Controlled human malaria infection
Clinical trial
description 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. 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. 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. 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. ClinicalTrials.gov and .
publishDate 2015
dc.date.none.fl_str_mv 2
2015-01-01
2015
2015-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/254352
https://dx.doi.org/urn:doi:10.1186/s12936-015-0628-0
url https://ddd.uab.cat/record/254352
https://dx.doi.org/urn:doi:10.1186/s12936-015-0628-0
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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