{
  "abstract": "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.\n\nOne Sentence SummaryPfSPZ-LARC2 Vaccine, a replication-competent genetically attenuated malaria sporozoite vaccine, was safe and immunogenic in 1-48-year-old Burkinabes",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "name": "Sodiomon B. Sirima",
      "orcid": "0000-0002-0972-4211"
    },
    {
      "name": "Thomas L Richie",
      "orcid": "0000-0002-2946-5456"
    },
    {
      "name": "Alphonse Ouedraogo"
    },
    {
      "name": "Ben I. Soulama"
    },
    {
      "name": "Aminata R. Zou"
    },
    {
      "name": "Issa Nebié"
    },
    {
      "name": "KC Natasha"
    },
    {
      "name": "Nelly Camargo"
    },
    {
      "name": "Debashree Goswami"
    },
    {
      "name": "Jean Moïse T. Kabore"
    },
    {
      "name": "Nafissatou Kirakoya"
    },
    {
      "name": "Rolel K. Mbaiasra"
    },
    {
      "name": "Sem Ezinmegnon"
    },
    {
      "name": "Emilie S. Badoum"
    },
    {
      "name": "Sinndia Y. Ouedraogo"
    },
    {
      "name": "Noelie B. Henry"
    },
    {
      "name": "Jean B. Yaro"
    },
    {
      "name": "Thabo Mabuka"
    },
    {
      "name": "Tooba Murshedkar"
    },
    {
      "name": "Yonas Abebe"
    },
    {
      "name": "Diana Perez"
    },
    {
      "name": "Eric R. James"
    },
    {
      "name": "Nana Minkah"
    },
    {
      "name": "Ashley M. Vaughan"
    },
    {
      "name": "Matthew B. Laurens",
      "orcid": "0000-0003-3874-581X"
    },
    {
      "name": "B. Kim Lee Sim",
      "orcid": "0000-0002-8598-8905"
    },
    {
      "name": "Stefan H. I. Kappe",
      "orcid": "0000-0003-1540-1731"
    },
    {
      "name": "Alfred B. Tiono"
    },
    {
      "name": "Stephen L. Hoffman",
      "orcid": "0000-0002-0700-9505"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7edxbqnvk36yg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.26365330",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1.full",
  "id": "7edxbqnvk36yg",
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  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7223122650",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1.full.pdf",
  "pmcid": "PMC13738891",
  "pmid": "42996307",
  "published": "2026-10-16",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/7edxbqnvk36yg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:25Z",
      "native_id": "10.64898/2026.10.16.26365330",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.16.26365330v1"
    },
    {
      "first_seen": "2026-11-09T12:23:48Z",
      "native_id": "PMC13738891",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria",
  "title_text": "First-in-human trial in Burkinabe adults and children of replication-competent, genetically attenuated PfSPZ-LARC2 Vaccine for malaria",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:48Z",
  "url": "https://research.draconitic.com/paper/7edxbqnvk36yg",
  "venue": "medRxiv",
  "versions": []
}