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疟疾疫苗RTS,S/AS01在小鼠体内诱导产生的抗体介导保护作用的表位特异性

Epitope specificity of antibody-mediated protection induced in mice by the malaria vaccine RTS,S/AS01.

作者信息

Flores-Garcia Yevel, Salgado-Jimenez Berenice, Park Minah, Mathis-Torres Shamika, Locke Emily, MacGill Randall S, Moskovitz Re'em, Wilson Ian A, Zavala Fidel

机构信息

Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Center for Vaccine Innovation and Access, PATH, Washington, DC, USA.

出版信息

NPJ Vaccines. 2025 May 20;10(1):101. doi: 10.1038/s41541-025-01162-5.

DOI:10.1038/s41541-025-01162-5
PMID:40394009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12092751/
Abstract

Antibodies induced by the malaria vaccine RTS,S/AS01 neutralize infectivity of transgenic sporozoites expressing Plasmodium falciparum CSP (PfCSP). These antibodies recognize the junctional, minor repeats, central repeats, and C-term regions of this antigen. The epitope specificity of antibodies mediating protection in mice was characterized in vivo using transgenic sporozoites expressing restricted antigenic portions of PfCSP. In this model, we found protection is mediated mostly by antibodies specific for the central repeats.

摘要

疟疾疫苗RTS,S/AS01诱导产生的抗体可中和表达恶性疟原虫环子孢子蛋白（PfCSP）的转基因子孢子的感染性。这些抗体可识别该抗原的连接区、小重复序列、中央重复序列和C端区域。利用表达PfCSP有限抗原部分的转基因子孢子在体内对介导小鼠保护作用的抗体的表位特异性进行了表征。在该模型中，我们发现保护作用主要由针对中央重复序列的特异性抗体介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/12092751/1fb7f9e793b1/41541_2025_1162_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/12092751/2d0f4bf23b95/41541_2025_1162_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/12092751/1fb7f9e793b1/41541_2025_1162_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/12092751/2d0f4bf23b95/41541_2025_1162_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/12092751/1fb7f9e793b1/41541_2025_1162_Fig2_HTML.jpg

相似文献

[1]
Epitope specificity of antibody-mediated protection induced in mice by the malaria vaccine RTS,S/AS01.

NPJ Vaccines. 2025-5-20

[2]
ProC6C, a novel multi-stage malaria vaccine, elicits functional antibodies against the minor and central repeats of the Circumsporozoite Protein in human adults.

Front Immunol. 2024

[3]
Structural ordering of the circumsporozoite protein repeats by inhibitory antibody 3D11.

Elife. 2020-11-30

[4]
The biological function of antibodies induced by the RTS,S/AS01 malaria vaccine candidate is determined by their fine specificity.

Malar J. 2016-5-31

[5]
A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum.

Malar J. 2016-11-8

[6]
Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers.

Hum Vaccin Immunother. 2020

[7]
Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein.

PLoS Pathog. 2021-12

[8]
Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine.

Malar J. 2013-4-22

[9]
The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.

PLoS Pathog. 2021-11

[10]
RTS,S/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally.

Sci Rep. 2018-4-26

本文引用的文献

[1]
Establishing RTS,S/AS01 as a benchmark for comparison to next-generation malaria vaccines in a mouse model.

NPJ Vaccines. 2024-2-10

[2]
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

[3]
A candidate antibody drug for prevention of malaria.

Nat Med. 2024-1

[4]
Novel antibody competition binding assay identifies distinct serological profiles associated with protection.

Front Immunol. 2023

[5]
Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.

N Engl J Med. 2022-11-17

[6]
Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria.

N Engl J Med. 2022-8-4

[7]
A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.

PLoS Pathog. 2022-3

[8]
Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein.

PLoS Pathog. 2021-12

[9]
The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.

PLoS Pathog. 2021-11

[10]
A Monoclonal Antibody for Malaria Prevention.

N Engl J Med. 2021-8-26

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