For a vaccine marketed as tetravalent protection against all four dengue serotypes, the actual breadth of immune coverage in dengue-naïve adults appears strikingly narrow — a gap that carries real implications for the hundreds of millions of people in dengue-endemic zones who may receive this shot without prior infection history.
This longitudinal preprint study enrolled 110 adults from a dengue-endemic setting and tracked humoral and cellular immune responses before and up to five months after Qdenga (TAK-003) vaccination. Participants were stratified by baseline dengue serostatus, sex, and age — notably including adults 65 and older, a group historically excluded from efficacy trials. Among dengue-naïve individuals, only 8% developed neutralizing antibody responses against all four serotypes. Roughly one-third of naïve recipients responded to just a single serotype — almost always DENV-2, the live-attenuated backbone on which Qdenga is built. Previously exposed individuals fared better in breadth, but even among seropositive recipients, DENV-4 neutralization remained consistently poor across the entire cohort. Both B cell activation and T cell memory formation were detectable across groups, suggesting cellular immunity is induced even when humoral breadth is limited.
These findings sharpen a long-standing concern in dengue vaccinology: immune imprinting, where prior serotype-specific exposure biases the subsequent immune response, may be as consequential for vaccine efficacy as it is for natural infection. The near-exclusive DENV-2 skewing in naïve individuals reflects the intrinsic immunodominance of the vaccine backbone rather than balanced tetravalent induction. This is not entirely unexpected — Sanofi's Dengvaxia faced analogous serotype coverage debates — but quantifying the gap so precisely in a real-world-adjacent cohort is meaningful. The consistent DENV-4 blind spot is particularly concerning given that serotype distribution shifts seasonally and geographically. As a preprint, these findings await peer review, and the five-month follow-up window does not capture long-term antibody kinetics. Still, the study challenges assumptions about Qdenga's population-level protective breadth, particularly for naïve recipients who represent a major deployment target.