{
  "abstract": "Early-phase trials of candidate malaria interventions in endemic areas often use \"time-to-first\" infection as a primary efficacy endpoint. This approach does not assess infection risk after the initial infection, and its censoring of trial participants after their first infection can introduce bias by removing more high-risk participants from control than treatment arms over time. Efficacy estimate precision may also decline as risk set size decreases. Here we assessed the utility of genotyping all infections in an intervention trial to determine the total infection incidence in each participant for the full follow-up period. Specifically, we genotyped all Plasmodium falciparum infections detected in a previously-reported phase 2 trial of the antimalarial monoclonal antibody CIS43LS in 330 Malian adults. We determined the molecular force of infection (molFOI; rate of new P. falciparum strains) for each participant, expressing efficacy as the percent molFOI reduction in CIS43LS versus placebo arms (EffmolFOI). Six-month EffmolFOI was 86.5% (95% CI: 80.1-90.8) and 70.7% (61.0-78.0) for the 40 mg/kg and 10 mg/kg doses, respectively. These estimates are similar to those from time-to-first infection analysis, but more precise when analyzing efficacy by trial-month and when stratifying by P. falciparum infection-status at enrollment. Participants infected at enrollment had lower EffmolFOI and acquired infections earlier in the trial, creating systematic differences in risk composition between arms over time. Genotyping showed no evidence for escape-polymorphisms in the CIS43LS epitope. These results demonstrate how genotypic endpoints can provide a more comprehensive understanding of candidate malaria interventions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health; Boston, MA, USA"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "P. Schwabl"
    },
    {
      "name": "A. Niangaly"
    },
    {
      "name": "W. Nickols"
    },
    {
      "name": "V. Callier"
    },
    {
      "name": "A. Mateja"
    },
    {
      "name": "K. Kayentao"
    },
    {
      "name": "A. Ongoiba"
    },
    {
      "name": "J. Skinner"
    },
    {
      "name": "A. C. Preston"
    },
    {
      "name": "S. Doumbo"
    },
    {
      "name": "D. Doumtabe"
    },
    {
      "name": "J. E. Amaya-Romero"
    },
    {
      "name": "K. K. Kelley"
    },
    {
      "name": "S. Li"
    },
    {
      "name": "M. Laws"
    },
    {
      "name": "M. E. Peterson"
    },
    {
      "name": "T. M. Tran"
    },
    {
      "name": "S. C. Murphy"
    },
    {
      "name": "B. Traore"
    },
    {
      "name": "R. A. Seder"
    },
    {
      "name": "P. D. Crompton"
    },
    {
      "name": "G. E. Potter"
    },
    {
      "affs": [
        0
      ],
      "name": "D. E. Neafsey"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/732hq9ta7g3hy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.26367264",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367264v1.full",
  "id": "732hq9ta7g3hy",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367264v1",
  "language": null,
  "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": [
    [
      "medrxiv",
      "infectious diseases"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367264v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/732hq9ta7g3hy.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:20:55Z",
      "native_id": "10.64898/2026.11.04.26367264",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367264v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Genotypic infection endpoint analysis to understand efficacy and escape potential of the malaria monoclonal antibody CIS43LS",
  "title_text": "Genotypic infection endpoint analysis to understand efficacy and escape potential of the malaria monoclonal antibody CIS43LS",
  "type": "preprint",
  "updated_at": "2026-11-08T00:20:56Z",
  "url": "https://research.draconitic.com/paper/732hq9ta7g3hy",
  "venue": "medRxiv",
  "versions": []
}