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Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.

作者信息

Langowski Mark D, Francica Joseph R, Roederer Alex L, Hurlburt Nicholas K, Rodarte Justas V, Da Silva Pereira Lais, Flynn Barbara J, Bonilla Brian, Dillon Marlon, Kiyuka Patience, Ravichandran Rashmi, Weidle Connor, Carter Lauren, Rao Mangala, Matyas Gary R, Pepper Marion, Idris Azza H, Seder Robert A, Pancera Marie, King Neil P

机构信息

Institute for Protein Design, University of Washington, Seattle, WA, USA.

Department of Biochemistry, University of Washington, Seattle, WA, USA.

出版信息

NPJ Vaccines. 2025 May 5;10(1):87. doi: 10.1038/s41541-025-01140-x.


DOI:10.1038/s41541-025-01140-x
PMID:40325041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12053698/
Abstract

A vaccine that provides robust, durable protection against malaria remains a global health priority. Although a breakthrough in the fight against malaria has recently been achieved by the licensure of two vaccines based on the circumsporozoite protein (CSP), the effectiveness and durability of protection can still be improved. Both vaccines contain a portion of CSP that does not include epitopes targeted by recently identified, potently protective monoclonal antibodies, suggesting that newer immunogens can expand the breadth of immunity and potentially increase protection. Here we explored >100 alternative CSP-based immunogens and evaluated the immunogenicity and protection of a large number of candidates, comparing several to the licensed R21 vaccine. The data highlight several general features that improve the stability and immunogenicity of CSP-based vaccines, such as inclusion of the C-terminal domain and high-density display on protein nanoparticle scaffolds. We also identify antigen design strategies that do not warrant further exploration, such as synthetic repeat regions that include non-native repeat cadences. The benchmark R21 vaccine outperformed our best immunogen for immunogenicity and protection. Overall, our data provide valuable insights on the inclusion of junctional region epitopes that will guide the development of potent and durable vaccines against malaria.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/53d20f75b44a/41541_2025_1140_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/250b95ead2ec/41541_2025_1140_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/dc5e1c9fd700/41541_2025_1140_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/c15106e08756/41541_2025_1140_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/a2055d4bb41b/41541_2025_1140_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/53d20f75b44a/41541_2025_1140_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/250b95ead2ec/41541_2025_1140_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/dc5e1c9fd700/41541_2025_1140_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/c15106e08756/41541_2025_1140_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/a2055d4bb41b/41541_2025_1140_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ae/12053698/53d20f75b44a/41541_2025_1140_Fig5_HTML.jpg

相似文献

[1]
Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.

NPJ Vaccines. 2025-5-5

[2]
Strategic Variants of CSP Delivered as SynDNA Vaccines Demonstrate Heterogeneity of Immunogenicity and Protection from Infection in a Murine Model.

Infect Immun. 2021-9-16

[3]
Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein.

PLoS Pathog. 2021-12

[4]
Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children.

BMC Med. 2018-10-31

[5]
Restricted valency (NPNA) repeats and junctional epitope-based circumsporozoite protein vaccines against Plasmodium falciparum.

NPJ Vaccines. 2022-1-27

[6]
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[7]
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[8]
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Vaccines (Basel). 2021-3-18

[9]
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[10]
Human responses to the DNA prime/chimpanzee adenovirus (ChAd63) boost vaccine identify CSP, AMA1 and TRAP MHC Class I-restricted epitopes.

PLoS One. 2025-2-13

引用本文的文献

[1]
A combined designed CSP and Pfs48/45 infection and transmission blocking vaccine for malaria.

NPJ Vaccines. 2025-9-2

本文引用的文献

[1]
Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Cell. 2025-2-20

[2]
Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

N Engl J Med. 2024-5-2

[3]
Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial.

Lancet. 2024-2-10

[4]
Antigen spacing on protein nanoparticles influences antibody responses to vaccination.

Cell Rep. 2023-12-26

[5]
Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.

Cell Rep. 2023-12-26

[6]
Biophysical characterization of the Plasmodium falciparum circumsporozoite protein's N-terminal domain.

Protein Sci. 2024-1

[7]
Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.

Cell Rep. 2023-11-28

[8]
Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms.

Cell Rep Med. 2023-11-21

[9]
Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences.

Vaccine. 2023-11-2

[10]
Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera.

Nat Commun. 2023-10-4

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