First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria

@misc{sirima2026firstinhuman,
  title = {{First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria}},
  author = {Sodiomon B. Sirima and Thomas L Richie and Alphonse Ouedraogo and Ben I. Soulama and Aminata R. Zou and Issa Nebié and KC Natasha and Nelly Camargo and Debashree Goswami and Jean Moïse T. Kabore and Nafissatou Kirakoya and Rolel K. Mbaiasra and Sem Ezinmegnon and Emilie S. Badoum and Sinndia Y. Ouedraogo and Noelie B. Henry and Jean B. Yaro and Thabo Mabuka and Tooba Murshedkar and Yonas Abebe and Diana Perez and Eric R. James and Nana Minkah and Ashley M. Vaughan and Matthew B. Laurens and B. Kim Lee Sim and Stefan H. I. Kappe and Alfred B. Tiono and Stephen L. Hoffman},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.16.26365330},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1},
  note = {CC BY-NC},
}

TY  - UNPB
TI  - First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria
AU  - Sodiomon B. Sirima
AU  - Thomas L Richie
AU  - Alphonse Ouedraogo
AU  - Ben I. Soulama
AU  - Aminata R. Zou
AU  - Issa Nebié
AU  - KC Natasha
AU  - Nelly Camargo
AU  - Debashree Goswami
AU  - Jean Moïse T. Kabore
AU  - Nafissatou Kirakoya
AU  - Rolel K. Mbaiasra
AU  - Sem Ezinmegnon
AU  - Emilie S. Badoum
AU  - Sinndia Y. Ouedraogo
AU  - Noelie B. Henry
AU  - Jean B. Yaro
AU  - Thabo Mabuka
AU  - Tooba Murshedkar
AU  - Yonas Abebe
AU  - Diana Perez
AU  - Eric R. James
AU  - Nana Minkah
AU  - Ashley M. Vaughan
AU  - Matthew B. Laurens
AU  - B. Kim Lee Sim
AU  - Stefan H. I. Kappe
AU  - Alfred B. Tiono
AU  - Stephen L. Hoffman
PY  - 2026
DA  - 2026/10/16
PB  - medRxiv
DO  - 10.64898/2026.10.16.26365330
UR  - https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1
AB  - The World Health Organization has called for malaria vaccines with > 90% efficacy against Plasmodium falciparum (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 SummaryPfSPZ-LARC2 Vaccine, a replication-competent genetically attenuated malaria sporozoite vaccine, was safe and immunogenic in 1-48-year-old Burkinabes
ER  -