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
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C1q
Acceso en línea:https://doaj.org/article/5ae092d9be98448ebee98ac018224269
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Sumario: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>.