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

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; ClinicalTrials.gov: NCT01511250), pre- and post-vaccination. 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 post-vaccination, 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.


CONCLUSION
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.