First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria
Year: 2026
Type: preprint
Study design: Clinical Trial
Abstract: (Pf) infection. The live, non-attenuated PfSPZ-CVac (chloroquine) vaccine provides the strongest protection against controlled human malaria infection (CHMI). Its 100% protective efficacy at 12 weeks against genetically distant Pf stems from a highly amplified immune stimulus. After inoculation, each invading sporozoite (SPZ) replicates up to 50,000 times within a hepatocyte. Over six days of development, these parasites express thousands of distinct proteins, presenting a vast and diverse array of antigens to the host immune system. The late liver stage parasites then rupture into the bloodstream, where they are killed by the co-administered drug, chloroquine. To engineer a Pf parasite that develops to the late liver stage like PfSPZ-CVac (chloroquine), but then arrests before transitioning to the blood stage, two genes required for transition from non-pathogenic liver to pathogenic blood stages were identified and deleted, creating late-liver stage arresting, replication-competent (LARC) PfSPZ. In a first-in-human, randomized, double-blind, placebo-controlled clinical trial, we assessed PfSPZ-LARC2 Vaccine in 75 malaria-exposed Burkinabe 1-to 48-year-olds. No vaccine-strain breakthrough blood-stage infections were detected; safety and tolerability profiles were similar in vaccinees and placebo recipients; and the highest immunogenicity was observed in the youngest recipients. Based on these findings, PfSPZ-LARC2 Vaccine has progressed to Phase 2 testing with the goal of rapidly advancing this genetically attenuated whole parasite vaccine to licensure and deployment. One Sentence Summary: PfSPZ-LARC2 Vaccine, a replication-competent genetically attenuated malaria sporozoite vaccine, was safe and immunogenic in 1-48-year-old Burkinabes.
Source: medRxiv
Authors: Sodiomon B. Sirima, Thomas L Richie, Alphonse Ouedraogo, Ben I. Soulama, Aminata R. Zou, Issa Nebié, KC Natasha, Nelly Camargo, Debashree Goswami, Jean Moïse T. Kabore, Nafissatou Kirakoya, Rolel K. Mbaiasra, Sem Ezinmegnon, Emilie S. Badoum, Sinndia Y. Ouedraogo, Noelie B. Henry, Jean B. Yaro, Thabo Mabuka, Tooba Murshedkar, Yonas Abebe, Diana Perez, Eric R. James, Nana Minkah, Ashley M. Vaughan, Matthew B. Laurens, B. Kim Lee Sim, Stefan H. I. Kappe, Alfred B. Tiono, Stephen L. Hoffman
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223122650