Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System

Abstract Background Antibody-driven complement system (CS) activation has been associated with protection against symptomatic dengue virus (DENV) infection. Aggregation, opsonization, lysis, and phagocytosis are mechanisms triggered by antibody-antigen immunocomplexes following fixation of the compo...

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Published in:The Journal of infectious diseases 2023-05, Vol.227 (11), p.1282-1292
Main Authors: Nascimento, Eduardo J M, Norwood, Brooke, Kpamegan, Eloi, Parker, Allan, Fernandes, Jesuina, Perez-Guzman, Erick, Tricou, Vianney, Braun, Ralph, Sharma, Mayuri, Dean, Hansi J
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Neutralizing
Avidity
Classical pathway
Clinical trials
Complement activation
Complement C1q
Complement system
Complement System Proteins
Dengue
Dengue fever
Dengue Vaccines
Dengue Virus
Humans
Immunoglobulin G
Infections
Lysis
Major
Opsonization
Phagocytosis
Serotypes
Vaccines
Vaccines, Attenuated
Viruses
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Summary:Abstract Background Antibody-driven complement system (CS) activation has been associated with protection against symptomatic dengue virus (DENV) infection. Aggregation, opsonization, lysis, and phagocytosis are mechanisms triggered by antibody-antigen immunocomplexes following fixation of the component 1q (C1q) and activation of the classical pathway. As a result, DENV neutralization and clearance are facilitated, whereas antibody-dependent enhancement of infection is inhibited. We investigated the ability of antibodies produced in response to Takeda's dengue vaccine candidate, TAK-003, to fix C1q and activate CS. Methods Serum samples were collected from seronegative and seropositive participants in a phase 2 clinical trial (DEN-203), pre- and postvaccination. Samples were evaluated for the presence of complement-fixing antibodies (CFAs) against DENV using a Luminex multiplex-based immunoassay. Results TAK-003 elicited production of CFAs against all 4 DENV serotypes, which persisted for 1 year postvaccination, irrespective of baseline serostatus. CFA levels were correlated with neutralizing antibody titers and virus-binding total IgG and IgG1 concentrations. Furthermore, efficiency of CFA fixation was greater in samples with higher polyclonal IgG avidity. Conclusions These results indicate that antibodies produced after TAK-003 vaccination are functional in both activating CS and neutralizing virus infection by all DENV serotypes, which may contribute to efficacy of TAK-003. Clinical Trials Registration NCT01511250. Antibodies produced after vaccination with TAK-003 are functional in fixing and activating complement system on all dengue virus serotypes, which may contribute to the efficacy of TAK-003.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiac476