Evidence map›Paper›PMID 41253879›Full record

ArticleNPJ vaccines2025

mRNA delivery of circumsporozoite protein epitope-based malaria vaccines induces protection in a mouse model.

Nelson R Wu, Nathan Beutler, Xiaozhen Hu, Patrick D Skog, Alessia Liguori, Yevel Flores-Garcia, Laura Maiorino, Sierra Terada, Danny Lu, Yen-Chung Lai and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. 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
  3. Review
  4. Parasitology · 2026
    Review
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

27 authors.

Nelson R Wu *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nathan Beutler *Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Xiaozhen HuDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Patrick D SkogDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Alessia LiguoriDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Yevel Flores-GarciaJohns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Laura MaiorinoDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sierra TeradaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Danny LuDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Yen-Chung LaiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Justin NdihokubwayoDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Torben SchiffnerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Christopher A CottrellDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Saman EskandarzadehDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nushin AlaviDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Michael KubitzDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nicole PhelpsDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Ryan TingleDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Sam HodgesDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
John E YouhannaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Sonya AmirzehniDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Darrell J IrvineDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sunny HimansuModerna Inc., Cambridge, MA, USA.
Fidel ZavalaJohns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Thomas F RogersDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. trogers@scripps.edu.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. burton@scripps.edu.
William R SchiefDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.

Funding

Bill and Melinda Gates Foundation INV-056202Gates Foundation INV-001763
6 · The paper itself

Abstract

Malaria is a leading cause of disease in developing countries. The licensed malaria vaccines (RTS,S/AS01 and R21/Matrix-M) have shown significant efficacy in human phase 3 trials. Vaccination with radiation-attenuated sporozoites has achieved high levels of protection against malaria in controlled infection studies, although protection was more moderate in clinical trials conducted in malaria-endemic areas. RTS,S/AS01, and R21/Matrix-M contain the repeating NANP motif and the C-terminal domain of the dominant surface circumsporozoite protein (CSP) of Plasmodium falciparum (Pf) sporozoites, but do not include the CSP N-terminal domain or epitopes in the junctional region between the N-terminal domain and the NANP repeats. In pursuit of a second-generation malaria PfCSP vaccine that surpasses the protection elicited by attenuated sporozoites and current subunit vaccines, we developed self-assembling nanoparticle immunogens each displaying one or more of four different classes of PfCSP epitope regions: NANP-repeat epitopes, junctional region-repeat epitopes, and epitopes from the N-terminal and C-terminal domains. In a mouse model of malaria infection, immunization with protein nanoparticles displaying different CSP epitope regions showed a reduction in liver burden ranging from minimal to 90%, with N- and C-terminal domains providing little reduction, but a combination of junctional and NANP repeat epitopes providing a strong reduction. mRNA-delivered nanoparticle and membrane-anchored immunogens displaying both the junctional and NANP repeat epitopes were most effective, exhibiting 99% reduction in liver burden and sterilizing immunity from parasitemia in some mice. The mRNA immunogens represent promising candidates for rapid translation to human challenge studies and could be combined with T cell vaccines to comprise a potential next-generation malaria vaccine.

Identifiers

PMID41253879
PMCPMC12627087

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