Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus

Antibodies capable of activating the complement system (CS) when bound with antigen are referred to as “complement-fixing antibodies” and are involved in protection against <i>Flaviviruses</i>. A complement-fixing antibody test has been used in the past to measure the ability of dengue v...

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Autores principales:	Eduardo J. M. Nascimento, Brooke Norwood, Allan Parker, Ralph Braun, Eloi Kpamegan, Hansi J. Dean
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Luminex dengue virus C1q complement system complement-fixing antibodies classical pathway Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5ae092d9be98448ebee98ac018224269
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spelling	oai:doaj.org-article:5ae092d9be98448ebee98ac0182242692021-11-11T17:25:17ZDevelopment and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus10.3390/ijms2221120041422-00671661-6596https://doaj.org/article/5ae092d9be98448ebee98ac0182242692021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12004https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Antibodies capable of activating the complement system (CS) when bound with antigen are referred to as “complement-fixing antibodies” and are involved in protection against <i>Flaviviruses</i>. A complement-fixing antibody test has been used in the past to measure the ability of dengue virus (DENV)-specific serum antibodies to activate the CS. As originally developed, the test is time-consuming, cumbersome, and has limited sensitivity for DENV diagnosis. Here, we developed and characterized a novel multiplex anti-DENV complement-fixing assay based on the Luminex platform to quantitate serum antibodies against all four serotypes (DENV1-4) that activate the CS based on their ability to fix the complement component 1q (C1q). The assay demonstrated good reproducibility and showed equivalent performance to a DENV microneutralization assay that has been used to determine DENV serostatus. In non-human primates, antibodies produced in response to primary DENV1-4 infection induced C1q fixation on homologous and heterologous serotypes. Inter-serotype cross-reactivity was associated with homology of the envelope protein. Interestingly, the antibodies produced following vaccination against Zika virus fixed C1q on DENV. The anti-DENV complement fixing antibody assay represents an alternative approach to determine the quality of functional antibodies produced following DENV natural infection or vaccination and a biomarker for dengue serostatus, while providing insights about immunological cross-reactivity among different <i>Flaviviruses</i>.Eduardo J. M. NascimentoBrooke NorwoodAllan ParkerRalph BraunEloi KpameganHansi J. DeanMDPI AGarticleLuminexdengue virusC1qcomplement systemcomplement-fixing antibodiesclassical pathwayBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12004, p 12004 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Luminex dengue virus C1q complement system complement-fixing antibodies classical pathway Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Luminex dengue virus C1q complement system complement-fixing antibodies classical pathway Biology (General) QH301-705.5 Chemistry QD1-999 Eduardo J. M. Nascimento Brooke Norwood Allan Parker Ralph Braun Eloi Kpamegan Hansi J. Dean Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
description	Antibodies capable of activating the complement system (CS) when bound with antigen are referred to as “complement-fixing antibodies” and are involved in protection against <i>Flaviviruses</i>. A complement-fixing antibody test has been used in the past to measure the ability of dengue virus (DENV)-specific serum antibodies to activate the CS. As originally developed, the test is time-consuming, cumbersome, and has limited sensitivity for DENV diagnosis. Here, we developed and characterized a novel multiplex anti-DENV complement-fixing assay based on the Luminex platform to quantitate serum antibodies against all four serotypes (DENV1-4) that activate the CS based on their ability to fix the complement component 1q (C1q). The assay demonstrated good reproducibility and showed equivalent performance to a DENV microneutralization assay that has been used to determine DENV serostatus. In non-human primates, antibodies produced in response to primary DENV1-4 infection induced C1q fixation on homologous and heterologous serotypes. Inter-serotype cross-reactivity was associated with homology of the envelope protein. Interestingly, the antibodies produced following vaccination against Zika virus fixed C1q on DENV. The anti-DENV complement fixing antibody assay represents an alternative approach to determine the quality of functional antibodies produced following DENV natural infection or vaccination and a biomarker for dengue serostatus, while providing insights about immunological cross-reactivity among different <i>Flaviviruses</i>.
format	article
author	Eduardo J. M. Nascimento Brooke Norwood Allan Parker Ralph Braun Eloi Kpamegan Hansi J. Dean
author_facet	Eduardo J. M. Nascimento Brooke Norwood Allan Parker Ralph Braun Eloi Kpamegan Hansi J. Dean
author_sort	Eduardo J. M. Nascimento
title	Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title_short	Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title_full	Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title_fullStr	Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title_full_unstemmed	Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title_sort	development and characterization of a multiplex assay to quantify complement-fixing antibodies against dengue virus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5ae092d9be98448ebee98ac018224269
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Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus

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