Complete attenuation of Plasmodium falciparum sporozoites by atovaquone–proguanil
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.
DOI: 10.18452/35769
Authors: Borrmann, Steffen, Sulyok, Zita, Müller, Katja, Fendel, Rolf, Sulyok, Mihály, Friesen, Johannes, Lalremruata, Albert, Sandri, Thaisa Lucas, Nguyen, The Trong, Calle, Carlos Lamsfus, Knoblich, Annette, Sefried, Stephanie, Ibáñez, Javier, Lorenz, Freia-Raphaella, Heimann, Henri Lynn, Weller, David M, Steuder, Regina, Adukpo, Selorme, Granados Bayon, Patricia, Molnár, Zsófia, Esen, Meral, Metzger, Wolfram, James, Eric R, Ruben, Adam, Abebe, Yonas, Chakravarty, Sumana, Manoj, Anita, KC, Natasha, Murshedkar, Tooba, Hafalla, Julius C R, Woldearegai, Tamirat Gebru, O’Rourke, Fiona, Held, Jana, Billingsley, Pete, Sim, B Kim Lee, Richie, Thomas L, Hoffman, Stephen L, Kremsner, Peter G, Matuschewski, Kai, Mordmüller, Benjamin
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7125781087
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