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贝利斯和洛伊的添加剂和协同效应在疟原虫生长抑制 AMA1-RON2L,RH5,RIPR 和 CyRPA 抗体组合。

Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations.

机构信息

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA.

Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

出版信息

Sci Rep. 2020 Jul 16;10(1):11802. doi: 10.1038/s41598-020-67877-8.


DOI:10.1038/s41598-020-67877-8
PMID:32678144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7366652/
Abstract

Plasmodium invasion of red blood cells involves malaria proteins, such as reticulocyte-binding protein homolog 5 (RH5), RH5 interacting protein (RIPR), cysteine-rich protective antigen (CyRPA), apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2), all of which are blood-stage malaria vaccine candidates. So far, vaccines containing AMA1 alone have been unsuccessful in clinical trials. However, immunization with AMA1 bound with RON2L (AMA1-RON2L) induces better protection against P. falciparum malaria in Aotus monkeys. We therefore sought to determine whether combinations of RH5, RIPR, CyRPA and AMA1-RON2L antibodies improve their biological activities and sought to develop a robust method for determination of synergy or additivity in antibody combinations. Rabbit antibodies against AMA1-RON2L, RH5, RIPR or CyRPA were tested either alone or in combinations in P. falciparum growth inhibition assay to determine Bliss' and Loewe's additivities. The AMA1-RON2L/RH5 combination consistently demonstrated an additive effect while the CyRPA/RIPR combination showed a modest synergistic effect with Hewlett's [Formula: see text] Additionally, we provide a publicly-available, online tool to aid researchers in analyzing and planning their own synergy experiments. This study supports future blood-stage vaccine development by providing a solid methodology to evaluate additive and/or synergistic (or antagonistic) effect of vaccine-induced antibodies.

摘要

疟原虫入侵红细胞涉及疟原蛋白,如网织红细胞结合蛋白同源物 5(RH5)、RH5 相互作用蛋白(RIPR)、富含半胱氨酸的保护性抗原(CyRPA)、顶膜抗原 1(AMA1)和 泡颈蛋白 2(RON2),它们都是血期疟疾疫苗候选物。到目前为止,仅含有 AMA1 的疫苗在临床试验中都不成功。然而,用 AMA1 与 RON2L(AMA1-RON2L)免疫可在食蟹猴中更好地预防恶性疟原虫疟疾。因此,我们试图确定 RH5、RIPR、CyRPA 和 AMA1-RON2L 抗体的组合是否能提高它们的生物学活性,并寻求开发一种用于确定抗体组合协同作用或相加作用的稳健方法。针对 AMA1-RON2L、RH5、RIPR 或 CyRPA 的兔抗体分别或组合用于恶性疟原虫生长抑制试验,以确定 Bliss 和 Loewe 的相加性。AMA1-RON2L/RH5 组合始终表现出相加作用,而 CyRPA/RIPR 组合与 Hewlett 的 [公式:见文本] 具有适度的协同作用。此外,我们提供了一个公开的在线工具,以帮助研究人员分析和计划他们自己的协同实验。这项研究通过提供一种评估疫苗诱导的抗体的相加和/或协同(或拮抗)作用的可靠方法,为未来的血期疫苗开发提供支持。

相似文献

[1]
Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations.

Sci Rep. 2020-7-16

[2]
Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits Detectable Levels of Invasion-Inhibitory Antibodies during Natural Infection in Humans.

Infect Immun. 2022-1-25

[3]
RH5.1-CyRPA-Ripr antigen combination vaccine shows little improvement over RH5.1 in a preclinical setting.

Front Cell Infect Microbiol. 2022

[4]
Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Nat Commun. 2024-6-7

[5]
Identification and Immune Assessment of T Cell Epitopes in Five Blood Stage Antigens to Facilitate Vaccine Candidate Selection and Optimization.

Front Immunol. 2021

[6]
Functional Comparison of Blood-Stage Malaria Vaccine Candidate Antigens.

Front Immunol. 2019-6-4

[7]
Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.

Nature. 2018-12-12

[8]
The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target.

Trends Parasitol. 2020-4-28

[9]
Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies.

Cell Rep Med. 2021-7-20

[10]
Immunoglobulin G subclass and antibody avidity responses in Malian children immunized with Plasmodium falciparum apical membrane antigen 1 vaccine candidate FMP2.1/AS02.

Malar J. 2019-1-18

引用本文的文献

[1]
A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.

Cell Rep Med. 2025-3-18

[2]
Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates.

NPJ Vaccines. 2024-10-24

[3]
Leveraging Immunofocusing and Virus-like Particle Display to Enhance Antibody Responses to the Malaria Blood-Stage Invasion Complex Antigen PfCyRPA.

Vaccines (Basel). 2024-7-30

[4]
Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

Cell. 2024-9-5

[5]
Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Nat Commun. 2024-6-7

[6]
Interactions of plumbagin with five common antibiotics against Staphylococcus aureus in vitro.

PLoS One. 2024-1-26

[7]
The malaria blood stage antigen PfCyRPA formulated with the TLR-4 agonist adjuvant GLA-SE elicits parasite growth inhibitory antibodies in experimental animals.

Malar J. 2023-7-15

[8]
Assessment of precision in growth inhibition assay (GIA) using human anti-PfRH5 antibodies.

Malar J. 2023-5-19

[9]
A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine.

Immunity. 2023-2-14

[10]
RH5.1-CyRPA-Ripr antigen combination vaccine shows little improvement over RH5.1 in a preclinical setting.

Front Cell Infect Microbiol. 2022

本文引用的文献

[1]
Functional Comparison of Blood-Stage Malaria Vaccine Candidate Antigens.

Front Immunol. 2019-6-4

[2]
Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

Cell. 2019-6-13

[3]
Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes.

Cell Microbiol. 2019-4-24

[4]
Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.

Nature. 2018-12-12

[5]
Additive Dose Response Models: Explicit Formulation and the Loewe Additivity Consistency Condition.

Front Pharmacol. 2018-2-6

[6]
Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions.

JCI Insight. 2017-11-2

[7]
Synergistic malaria vaccine combinations identified by systematic antigen screening.

Proc Natl Acad Sci U S A. 2017-10-23

[8]
A malaria vaccine protects monkeys against virulent infection.

NPJ Vaccines. 2017

[9]
The Molecular Basis of Erythrocyte Invasion by Malaria Parasites.

Cell Host Microbe. 2017-8-9

[10]
Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine.

PLoS One. 2017-3-10

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