Evidence map›Paper›PMID 32946741›Full record

ArticleImmunity2020

A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver.

Lawrence T Wang, Lais S Pereira, Yevel Flores-Garcia, James O'Connor, Barbara J Flynn, Arne Schön, Nicholas K Hurlburt, Marlon Dillon, Annie S P Yang, Amanda Fabra-García and 21 more

Open access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
13.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 158 citations in OpenAlex.

  1. Trial
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  7. Protective near-germline antibodies to malaria elicited by RTS,S/AS01bioRxiv : the preprint server for biology · 2026
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  15. Deep learning-enabled scaffolding of spatial arrays of PfCSP epitopes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Review
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 8 institutions in 5 countries.

Lawrence T WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lais S PereiraVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Yevel Flores-GarciaMalaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
James O'ConnorDepartment of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia; The Australian National University Medical School, Canberra, ACT 2601, Australia.
Barbara J FlynnVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Arne SchönDepartment of Biology, Johns Hopkins University, Baltimore, MD 21205, USA.
Nicholas K HurlburtVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Marlon DillonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Annie S P YangRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Amanda Fabra-GarcíaRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Azza H IdrisVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Bryan T MayerVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Monica W GerberVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Raphael GottardoVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Rosemarie D MasonVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole CavettVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Reid B BallardVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Neville K KisaluVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Alvaro Molina-CruzLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Jorgen NelsonDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Rachel VisteinVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Carolina Barillas-MuryLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Rogerio AminoUnit of Malaria Infection and Immunity, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France.
David BakerDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Neil P KingDepartment of Biochemistry and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Robert W SauerweinRadboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Marie PanceraVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Ian A CockburnDepartment of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.
Fidel ZavalaMalaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Joseph R FrancicaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Robert A SederVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rseder@mail.nih.gov.
National Institutes of Health · USFred Hutch Cancer Center · USJohns Hopkins University · USRadboud University Nijmegen · NLUniversity of Washington · USAustralian National University · AUCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAInstitut Pasteur · FR

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Development of Pre-Erythrocytic Malaria Vaccines and antibodiesZIAAI005107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SEDER, ROBERT A · 2010 to 2025
$20.7M
Monoclonal antibody isolation and characterizationZIAAI005126 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MASON, ROSEMARIE · 2015 to 2025
$10.1M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA AI005137NCI NIH HHS HHSN261200800001ENIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

Discovering potent human monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on sporozoites (SPZ) and elucidating their mechanisms of neutralization will facilitate translation for passive prophylaxis and aid next-generation vaccine development. Here, we isolated a neutralizing human mAb, L9 that preferentially bound NVDP minor repeats of PfCSP with high affinity while cross-reacting with NANP major repeats. L9 was more potent than six published neutralizing human PfCSP mAbs at mediating protection against mosquito bite challenge in mice. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound PfCSP with two binding events and mediated protection by killing SPZ in the liver and by preventing their egress from sinusoids and traversal of hepatocytes. This study defines the subdominant PfCSP minor repeats as neutralizing epitopes, identifies an in vitro biophysical correlate of SPZ neutralization, and demonstrates that the liver is an important site for antibodies to prevent malaria.

Indexed as

AdolescentAdultAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ProtozoanAntimalarialsCell LineCell Line, TumorEpitopesFemaleHEK293 CellsHepatocytesHumansLiverMalariaAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ProtozoanAntimalarialsEpitopesMalaria VaccinesProtozoan Proteinscircumsporozoite proteinmalaria vaccinesMonoclonal antibodiesNVDP minor repeatspassive transferPlasmodium falciparumsporozoites

Identifiers

PMID32946741
PMCPMC7572793
OpenAlexW3087379792

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.