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一种用于疟疾的联合设计的CSP和Pfs48/45感染及传播阻断疫苗。

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

作者信息

Gupta Richi, Dickey Thayne H, Salinas Nichole D, Patel Palak N, Ma Rui, Shi Dashuang, Singleton Myesha, Ouahes Tarik, Pham Thao P, Miura Kazutoyo, Long Carole A, Lambert Lynn E, Tolia Niraj H

机构信息

Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

出版信息

NPJ Vaccines. 2025 Sep 2;10(1):208. doi: 10.1038/s41541-025-01262-2.


DOI:10.1038/s41541-025-01262-2
PMID:40897705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12405497/
Abstract

The multiple stages of the malaria parasite life cycle hampers vaccine development. Combining a pre-erythrocytic antigen with a transmission-blocking antigen would target two independent stages of the life cycle for disease control, resulting in a multistage vaccine that can prevent infection and disease transmission simultaneously. Here, we generated a self-assembled ferritin nanoparticle vaccine that simultaneously presents designed immunogens CSPj5c and 17-4 from the infection-blocking circumsporozoite and the transmission-blocking Pfs48/45 antigens. These immunogens were designed, through structure-based approaches, to retain protective epitopes and confer protection upon vaccination. Immunization with CSPj5c-17-4-ferritin nanoparticles conferred protection against challenge with transgenic sporozoites expressing Plasmodium falciparum CSP in mice, and purified IgGs from immunized rabbits elicited potent transmission-reducing activity. Addition of the engineered 17-4 improved the immune responses to CSPj5c and protection from sporozoite challenge. CSPj5c-17-4-ferritin is therefore a promising multistage malaria vaccine with a potential role in malaria control.

摘要

疟原虫生命周期的多个阶段阻碍了疫苗的研发。将一种前体红细胞期抗原与一种传播阻断抗原相结合,将针对生命周期中两个独立阶段进行疾病控制,从而产生一种能够同时预防感染和疾病传播的多阶段疫苗。在此,我们制备了一种自组装铁蛋白纳米颗粒疫苗,该疫苗同时展示了来自感染阻断环子孢子蛋白的设计免疫原CSPj5c和来自传播阻断Pfs48/45抗原的17-4。这些免疫原通过基于结构的方法进行设计,以保留保护性表位并在接种疫苗后提供保护。用CSPj5c-17-4-铁蛋白纳米颗粒免疫可使小鼠免受表达恶性疟原虫CSP的转基因子孢子攻击,从免疫兔中纯化的IgG引发了强大的传播减少活性。添加工程化的17-4可改善对CSPj5c的免疫反应以及对子孢子攻击的保护作用。因此,CSPj5c-17-4-铁蛋白是一种有前景的多阶段疟疾疫苗,在疟疾控制中可能发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/ea5ec9b73fd2/41541_2025_1262_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/d3665a2748be/41541_2025_1262_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/dbfbd71e7477/41541_2025_1262_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/6ceb463eddcf/41541_2025_1262_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/90648d4fbf32/41541_2025_1262_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/ea5ec9b73fd2/41541_2025_1262_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/d3665a2748be/41541_2025_1262_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/dbfbd71e7477/41541_2025_1262_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/6ceb463eddcf/41541_2025_1262_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/90648d4fbf32/41541_2025_1262_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb5/12405497/ea5ec9b73fd2/41541_2025_1262_Fig5_HTML.jpg

相似文献

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

NPJ Vaccines. 2025-9-2

[2]
Evaluation of combination vaccines targeting transmission of Plasmodium falciparum and P. vivax.

Vaccine. 2024-8-30

[3]
Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria.

bioRxiv. 2025-5-30

[4]
Generation of a Transgenic Parasite Expressing Circumsporozoite Protein for Testing CSP-Based Malaria Vaccines in Non-Human Primates.

Vaccines (Basel). 2025-5-17

[5]
Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria.

NPJ Vaccines. 2025-7-30

[6]
Variable long-term protection by radiation-, chemo-, and genetically-attenuated Plasmodium berghei sporozoite vaccines.

Vaccine. 2023-12-12

[7]
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

[8]
Vaccines for preventing malaria.

Cochrane Database Syst Rev. 2003

[9]
WITHDRAWN: Vaccines for preventing malaria.

Cochrane Database Syst Rev. 2007-7-18

[10]
Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial.

Lancet Infect Dis. 2024-10

本文引用的文献

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

NPJ Vaccines. 2025-5-5

[2]
Magnitude and durability of ProC6C-AlOH/Matrix-M vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial.

Hum Vaccin Immunother. 2025-12

[3]
SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

Lancet Microbe. 2024-6

[4]
A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial.

BMC Med. 2024-4-23

[5]
Malaria vaccines for children: and now there are two.

Lancet. 2024-2-10

[6]
WHO prequalifies a second malaria vaccine, a significant milestone in prevention of the disease.

Saudi Med J. 2024-2

[7]
The 2023 WHO World malaria report.

Lancet Microbe. 2024-3

[8]
A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults.

J Clin Invest. 2024-4-1

[9]
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

NPJ Vaccines. 2024-1-10

[10]
A dual-antigen malaria vaccine targeting Pb22 and Pbg37 was able to induce robust transmission-blocking activity.

Parasit Vectors. 2023-12-14

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