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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 Flaviviruses. A complement-fixing antibody test has been used in the past to measure the ability of dengue virus (DENV)-specifi...

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Autores principales: Nascimento, Eduardo J. M., Norwood, Brooke, Parker, Allan, Braun, Ralph, Kpamegan, Eloi, Dean, Hansi J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584793/
https://www.ncbi.nlm.nih.gov/pubmed/34769432
http://dx.doi.org/10.3390/ijms222112004
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author Nascimento, Eduardo J. M.
Norwood, Brooke
Parker, Allan
Braun, Ralph
Kpamegan, Eloi
Dean, Hansi J.
author_facet Nascimento, Eduardo J. M.
Norwood, Brooke
Parker, Allan
Braun, Ralph
Kpamegan, Eloi
Dean, Hansi J.
author_sort Nascimento, Eduardo J. M.
collection PubMed
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 Flaviviruses. 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 Flaviviruses.
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spelling pubmed-85847932021-11-12 Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus Nascimento, Eduardo J. M. Norwood, Brooke Parker, Allan Braun, Ralph Kpamegan, Eloi Dean, Hansi J. Int J Mol Sci Article 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 Flaviviruses. 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 Flaviviruses. MDPI 2021-11-05 /pmc/articles/PMC8584793/ /pubmed/34769432 http://dx.doi.org/10.3390/ijms222112004 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nascimento, Eduardo J. M.
Norwood, Brooke
Parker, Allan
Braun, Ralph
Kpamegan, Eloi
Dean, Hansi J.
Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584793/
https://www.ncbi.nlm.nih.gov/pubmed/34769432
http://dx.doi.org/10.3390/ijms222112004
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