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- Title
Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus.
- Authors
Nascimento, Eduardo J. M.; Norwood, Brooke; Parker, Allan; Braun, Ralph; Kpamegan, Eloi; Dean, Hansi J.
- Abstract
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.
- Subjects
DENGUE viruses; IMMUNOGLOBULINS; COMPLEMENT activation; ARBOVIRUS diseases; ZIKA virus; ANTIBODY titer; ANTIBODY formation
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 21, p12004
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms222112004