Year: 2025
Type: article
Abstract: To develop a Plasmodium falciparum (Pf) vaccine that precludes replication inside the host for improved vaccine safety, we tested chemo-attenuation (CVac) of sporozoites (SPZ) with atovaquone–proguanil (AP). In mice, P. berghei sporozoites administered with AP invaded hepatocytes, arrested early, and induced robust protection, which correlated with parasite-specific effector-memory CD8+ T cell responses. In a clinical trial of PfSPZ-CVac (AP), in which three doses of 5.12 × 10 4 or 1.5 × 10 5 PfSPZ were administered by direct venous inoculation combined with oral single-dose AP (1000/400 mg), blood stage infections were fully prevented during immunisation. 2/8 and 2/10 of vaccinees, respectively, were protected when challenged with 3.2 × 10 3 PfSPZ 10 weeks later, inferior to PfSPZ-CVac (chloroquine/CQ) that allows in-host replication. Comparative analysis of responses to 228 Pf proteins revealed that protection with PfSPZ-CVac (CQ) was associated with antibodies to two liver-stage antigens (LISP2, LSA1) and a multi-stage antigen (PfMSP5), but not to the major surface protein PfCSP. The complete arrest of high numbers of Pf sporozoites by single-dose AP should allow a significant dose-frequency reduction of the current daily AP malaria chemoprophylaxis regimen.
Source: EMBO Molecular Medicine
Authors: Steffen Borrmann, Zita Sulyok, Katja Müller, Rolf Fendel, Mihály Sulyok, Johannes Friesen, Albert Lalremruata, Thaisa Lucas Sandri, The Trong Nguyen, Carlos Lamsfus Calle, Annette Knoblich, Stephanie Sefried, Javier Ibáñez, Freia-Raphaella Lorenz, Henri Lynn Heimann, David M Weller, Regina Steuder, Selorme Adukpo, Patricia Granados Bayon, Zsófia Molnár, Meral Esen, Wolfram Metzger, Eric R James, Adam Ruben, Yonas Abebe, Sumana Chakravarty, Anita Manoj, Natasha KC, Tooba Murshedkar, Julius C R Hafalla, Tamirat Gebru Woldearegai, Fiona O’Rourke, Jana Held, Pete Billingsley, B Kim Lee Sim, Thomas L Richie, Stephen L Hoffman, Peter G Kremsner, Kai Matuschewski, Benjamin Mordmüller
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Small Business Innovation Research, Deutsches Zentrum für Infektionsforschung, European Commission, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Max-Planck-Gesellschaft, National Institutes of Health, National Institute of Allergy and Infectious Diseases, European and Developing Countries Clinical Trials Partnership
Awards: Universal Attenuated Sporozoite Vaccine and Challenge System, G202574419, G2837046818, Plasmodium Falciparum Whole Sporozoite Malaria Vaccine, G3349051739, G343964332, G4931422650, G5216269092, G6250867368, G6722529557, G7200160227, G7478540455, Central Africa Training Platform for Clinical Research on infectious diseases, G9000334340
OpenAlex ID: W4414599095