Evidence map›Paper›PMID 35977542›Full record

ArticleImmunity2022

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses.

Brandon McLeod, Moustafa T Mabrouk, Kazutoyo Miura, Rashmi Ravichandran, Sally Kephart, Sophia Hailemariam, Thao P Pham, Anthony Semesi, Iga Kucharska, Prasun Kundu and 19 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
11.2field-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

35 citing papers in PubMed, 57 citations in OpenAlex.

  1. Trial
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  4. Improving the immunogenicity ofFrontiers in immunology · 2026
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  16. Malaria vaccines: a new era of prevention and control.Nature reviews. Microbiology · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 3 countries.

Brandon McLeodProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Moustafa T MabroukDepartment of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Kazutoyo MiuraLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA.
Rashmi RavichandranDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Sally KephartDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Sophia HailemariamProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Thao P PhamLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA.
Anthony SemesiProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Iga KucharskaProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Prasun KunduProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Wei-Chiao HuangDepartment of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Max JohnsonDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Alyssa BlackstoneDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Deleah PettieDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Michael MurphyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
John C KraftDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Elizabeth M LeafDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Yang JiaoDepartment of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Marga van de Vegte-BolmerDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Geert-Jan van GemertDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Jordache RamjithRadboud Institute for Health Sciences, Department for Health Evidence, Biostatistics Section, Radboud University Medical Center, Nijmegen, the Netherlands.
C Richter KingPATH's Malaria Vaccine Initiative, 455 Massachusetts Avenue NW Suite 1000, Washington, DC 20001, USA.
Randall S MacGillPATH's Malaria Vaccine Initiative, 455 Massachusetts Avenue NW Suite 1000, Washington, DC 20001, USA.
Yimin WuPATH's Malaria Vaccine Initiative, 455 Massachusetts Avenue NW Suite 1000, Washington, DC 20001, USA.
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Matthijs M JoreDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jonathan F LovellDepartment of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Jean-Philippe JulienProgram in Molecular Medicine, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: jean-philippe.julien@sickkids.ca.
University of Washington · USUniversity at Buffalo, State University of New York · USHospital for Sick Children · CARadboud University Medical Center · NLU.S. President's Malaria Initiative · USNational Institutes of Health · USUniversity of Toronto · CACanada Research Chairs · CARadboud University Nijmegen · NL

Funding

Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
Rationally-Designed, Spontaneous-Particleized Pfs48/45 for a Multivalent Malaria VaccineR01AI148557 · NIAID · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JULIEN, JEAN-PHILIPPE, LOVELL, JONATHAN F · 2020 to 2024
$2.1M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
NIAID NIH HHS R01 AI148557NIGMS NIH HHS T32 GM007750NIH HHS S10 OD012289
6 · The paper itself

Abstract

Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.

Indexed as

Malaria, FalciparumMalaria VaccinesAnimalsAntibodies, BlockingAntibodies, MonoclonalAntibodies, ProtozoanAntibody FormationAntigens, ProtozoanHumansMembrane GlycoproteinsMicePlasmodium falciparumProtozoan ProteinsVaccinationAntibodies, BlockingAntibodies, MonoclonalAntibodies, ProtozoanAntigens, ProtozoanMalaria VaccinesMembrane GlycoproteinsProtozoan Proteinsantibodiesmalariastructure-based immunogen design

Identifiers

PMID35977542
PMCPMC9487866
OpenAlexW4292055670

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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.