Antibodies Produced in Response to a Live-Attenuated Dengue Vaccine Are Functional in Activating the Complement System
Eduardo J. M. Nascimentoa✉, Brooke Norwooda, Eloi P. Kpameganb, Allan Parkera, Jesuina Fernandesa, Erick X. Pérez-Guzmána, Vianney Tricouc, Ralph Peter Brauna, Mayuri Sharmaa, Hansi J. Deand
- aVaccine Research and Analytics, Takeda Vaccines, Inc , Cambridge, Massachusetts , USA
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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.
TL;DRInvestigation of the ability of antibodies produced in response to Takeda's dengue vaccine candidate, TAK-003, to fix C1q and activate CS indicates that antibodies produced after Tak-003 vaccination are functional in both activating CS and neutralizing virus infection by all DENV serotypes. (Semantic Scholar)