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Safety, immunogenicity, and protective efficacy against controlled human malaria infection of Plasmodium falciparum sporozoites vaccine in Tanzanian adults

Jongo, Said A. and Shekalaghe, Seif A. and Church, L. W. Preston and Ruben, Adam J. and Schindler, Tobias and Zenklusen, Isabelle and Rutishauser, Tobias and Rothen, Julian and Tumbo, Anneth and Mkindi, Catherine and Mpina, Maximillian and Mtoro, Ali T. and Ishizuka, Andrew S. and Kassim, Kamaka Ramadhani and Milando, Florence A. and Qassim, Munira and Juma, Omar A. and Mwakasungula, Solomon and Simon, Beatus and James, Eric R. and Abebe, Yonas and Kc, Natasha and Chakravarty, Sumana and Saverino, Elizabeth and Bakari, Bakari M. and Billingsley, Peter F. and Seder, Robert A. and Daubenberger, Claudia and Sim, B. Kim Lee and Richie, Thomas L. and Tanner, Marcel and Abdulla, Salim and Hoffman, Stephen L.. (2018) Safety, immunogenicity, and protective efficacy against controlled human malaria infection of Plasmodium falciparum sporozoites vaccine in Tanzanian adults. American journal of tropical medicine and hygiene, 99 (2). pp. 338-349.

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Official URL: https://edoc.unibas.ch/65197/

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Abstract

We are using controlled human malaria infection (CHMI) by direct venous inoculation (DVI) of cryopreserved, infectious; Plasmodium falciparum; (Pf) sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing PfSPZ Vaccine to prevent malaria in Africa. Immunization with five doses at 0, 4, 8, 12, and 20 weeks of 2.7 × 10; 5; PfSPZ of PfSPZ Vaccine gave 65% vaccine efficacy (VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 52% (time to event) or 29% (proportional) VE over 24 weeks against naturally transmitted Pf in Malian adults. We assessed the identical regimen in Tanzanians for VE against PfSPZ Challenge. Twenty- to thirty-year-old men were randomized to receive five doses normal saline or PfSPZ Vaccine in a double-blind trial. Vaccine efficacy was assessed 3 and 24 weeks later. Adverse events were similar in vaccinees and controls. Antibody responses to Pf circumsporozoite protein were significantly lower than in malaria-naïve Americans, but significantly higher than in Malians. All 18 controls developed Pf parasitemia after CHMI. Four of 20 (20%) vaccinees remained uninfected after 3 week CHMI (; P; = 0.015 by time to event,; P; = 0.543 by proportional analysis) and all four (100%) were uninfected after repeat 24 week CHMI (; P; = 0.005 by proportional,; P; = 0.004 by time to event analysis).; Plasmodium falciparum; SPZ Vaccine was safe, well tolerated, and induced durable VE in four subjects. Controlled human malaria infection by DVI of PfSPZ Challenge appeared more stringent over 24 weeks than mosquito bite CHMI in United States or natural exposure in Malian adults, thereby providing a rigorous test of VE in Africa.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Biostatistics > Biostatistics Frequentist Modelling (Kwiatkowski)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Clinical Immunology (Daubenberger)
UniBasel Contributors:Schindler, Christian and Zenklusen, Isabelle and Rothen, Julian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Williams and Wilkins
ISSN:0002-9637
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:11 Sep 2018 09:11
Deposited On:11 Sep 2018 09:11

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