Evidence map›Paper›PMID 32150583›Full record

ArticlePLoS pathogens2020

Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein.

David Oyen, Jonathan L Torres, Phillip C Aoto, Yevel Flores-Garcia, Špela Binter, Tossapol Pholcharee, Sean Carroll, Sini Reponen, Rachael Wash, Qi Liang and 9 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

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  16. Review
  17. Restricted valency (NPNA)NPJ vaccines · 2022
    Article
  18. Structural basis ofeLife · 2022
    Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 2 countries.

David OyenDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0003-0137-8497
Phillip C AotoDepartment of Pharmacology, University of California at San Diego, La Jolla, California, United States of America.ORCID 0000-0001-6518-0899
Yevel Flores-GarciaMalaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Špela BinterKymab Ltd., The Bennet Building (B930), Babraham Research Campus, Cambridge, United Kingdom.ORCID 0000-0003-2335-6336
Tossapol PholchareeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0002-5347-1936
Sean CarrollAtreca Inc., South San Francisco, California, United States of America.
Sini ReponenAtreca Inc., South San Francisco, California, United States of America.
Rachael WashKymab Ltd., The Bennet Building (B930), Babraham Research Campus, Cambridge, United Kingdom.
Qi LiangKymab Ltd., The Bennet Building (B930), Babraham Research Campus, Cambridge, United Kingdom.
Franck LemialePATH's Malaria Vaccine Initiative, PATH Center for Vaccine Innovation and Access, Washington, United States of America.
Emily LockePATH's Malaria Vaccine Initiative, PATH Center for Vaccine Innovation and Access, Washington, United States of America.ORCID 0000-0003-1944-8473
Allan BradleyKymab Ltd., The Bennet Building (B930), Babraham Research Campus, Cambridge, United Kingdom.ORCID 0000-0002-2349-8839
C Richter KingPATH's Malaria Vaccine Initiative, PATH Center for Vaccine Innovation and Access, Washington, United States of America.
Daniel EmerlingAtreca Inc., South San Francisco, California, United States of America.
Paul KellamKymab Ltd., The Bennet Building (B930), Babraham Research Campus, Cambridge, United Kingdom.ORCID 0000-0003-3166-4734
Fidel ZavalaMalaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0001-7153-3769
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0002-6469-2419
Scripps Research Institute · USKymab (United Kingdom) · GBItasca Consultants (United States) · USJohns Hopkins University · USUniversity of California San Diego · USWellcome Sanger Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.

Indexed as

Binding Sites, AntibodyAnimalsAntibodies, Monoclonal, Murine-DerivedAntibodies, ProtozoanEpitopesFemaleMaleMiceMice, TransgenicPlasmodium falciparumProtozoan ProteinsStructure-Activity RelationshipAntibodies, Monoclonal, Murine-DerivedAntibodies, Protozoancircumsporozoite protein, ProtozoanEpitopesProtozoan Proteins

Identifiers

PMID32150583
PMCPMC7082059
OpenAlexW3009774424

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.