How Real-World Data Is Shaping the Future of Dengue Vaccination

Dengue cases continue to climb worldwide, fueled by expanding mosquito habitats, climate change, and increased urbanization. As countries grapple with larger and more frequent outbreaks, effective vaccines have become an increasingly important component of public health response alongside vector control and surveillance.

A recent real-world study from São Paulo, Brazil, evaluated the effectiveness of the TAK-003 dengue vaccine during one of the country's largest recent outbreaks. The findings showed strong protection against symptomatic disease and hospitalization following the recommended 2-dose series, while also suggesting meaningful protection after a single dose. Infection Control Today^® spoke with Julio Croda, MD, PhD, study investigator, researcher at the Oswaldo Cruz Foundation, and professor at the Federal University of Mato Grosso do Sul and the Yale School of Public Health, about what these results could mean for outbreak response, vaccination strategies, and the future of dengue prevention.

ICT: This study found that the TAK-003 dengue vaccine maintained strong protection against both symptomatic disease and hospitalization over 1 year during a major outbreak in São Paulo. From a public health perspective, how significant are these findings given the ongoing global rise in dengue transmission?

Julio Croda, MD, PhD: These findings are highly significant for global public health. We are currently witnessing an unprecedented surge in dengue transmission globally, driven by climate change, urbanization, and increased vector mobility, which is placing an immense strain on health care systems. While clinical trials offer critical efficacy data under controlled conditions, demonstrating that TAK-003 maintains robust effectiveness during a massive, real-world outbreak in São Paulo, which is the heart of Brazil's recent epidemic, provides the ultimate proof of concept.

Our study showed that a 2-dose schedule of TAK-003 yielded a vaccine effectiveness of 73.1% (95% CI 69.1–76.6) against symptomatic dengue and 87.9% (95% CI 73.0–94.6) against hospitalization. From a public health standpoint, preventing nearly 88% of hospitalizations during an active crisis is a game-changer. It directly translates into fewer severe cases, reduced mortality, and, crucially, the prevention of the collapse of hospital infrastructure and emergency departments during seasonal peaks.

ICT: One of the most notable findings was that even a single dose provided substantial protection against symptomatic dengue and severe outcomes. How could this influence outbreak response strategies or vaccination campaigns in regions experiencing surging case counts or limited health care resources?

JC: The durable protection offered by a single dose is one of the most operationally vital insights from this study. We found that a single dose of TAK-003 provided 59.2% (95% CI 56.1–62.0) protection against symptomatic disease and 74.6% (95% CI 62.7–82.7) against hospitalization, with no evidence of waning protection over the 1-year follow-up period, remaining at 73.8% at 270–364 days and 76.8% at 365 or more days after the first dose.

In regions facing explosive outbreaks or severe vaccine supply constraints, these data support a highly flexible public health strategy. Instead of holding back doses to guarantee a 2-dose regimen for a smaller cohort, health authorities could consider a rapid, single-dose campaign to broaden initial population coverage. This approach could quickly establish a baseline of protection, dramatically lower the peak of hospitalizations and save lives during an active surge. That said, it is essential to emphasize that the 2-dose schedule remains the gold standard for achieving optimal, long-term individual protection, particularly against hospitalization.

ICT: The study used a large real-world test-negative case-control design involving more than 166,000 tests. Why is real-world effectiveness data particularly important for dengue vaccines, and how does this type of evidence complement traditional clinical trial findings?

JC: Traditional randomized controlled trials are the gold standard for establishing biological efficacy, but they operate under idealized conditions with strict inclusion criteria and controlled exposure. Dengue, however, is highly dynamic; its transmission is characterized by rapid shifts in dominant serotypes, varying population immunity, and complex logistics in public health systems.

A real-world, test-negative case-control design involving over 166,000 tests (65,365 cases and 101,025 controls) provides the massive statistical power and diversity needed to evaluate how the vaccine performs in the context of a real epidemic. It accounts for real-world conditions, varying [adherence], and, importantly, the actual circulation of serotypes, such as the transition from DENV-1 and DENV-2 in 2024 to the rise of DENV-3 in 2025 in São Paulo. This real-world evidence complements clinical trials by confirming that the vaccine's efficacy successfully translates into a powerful, practical tool for public health control.

ICT: Dengue continues to place enormous strain on health care systems across tropical and subtropical regions, especially during large outbreaks. What operational or health care infrastructure challenges still complicate dengue prevention and response, even when effective vaccines are available?

JC: Vaccines are a powerful shield, but they do not solve the structural challenges of dengue control on their own. Several operational hurdles persist. First, logistics and distribution remain a challenge: implementing a multidose vaccine campaign in resource-limited settings requires robust registry systems to track individuals and minimize dropout rates between the first and second doses. Second, vector control limitations mean that vaccine rollout must coexist with, rather than replace, sustained environmental and vector control efforts against Aedes aegypti. Third, public communication and vaccine hesitancy require culturally sensitive outreach to build trust and ensure high uptake, particularly among adolescents. Finally, many endemic areas still lack real-time epidemiological and molecular surveillance, making it difficult to detect serotype shifts early or accurately measure localized vaccine impact.

ICT: Looking ahead, what additional surveillance, effectiveness, or durability data would you most like to see regarding TAK-003, particularly around long-term protection, different dengue serotypes, or broader implementation in endemic populations?

JC: As we move forward, there are 3 critical areas where we need more data. First, the long-term durability of single-dose protection: while our 1-year data is encouraging, we need to monitor these cohorts over multiple years to understand when—or if—protection begins to decline, which will inform whether a booster or the second dose is eventually required for those vaccinated during outbreak responses. Second, serotype-specific effectiveness: continued surveillance is needed to evaluate TAK-003's long-term real-world performance against DENV-3 and DENV-4, particularly because historical clinical trial data for these serotypes were more limited than for DENV-1 and DENV-2. Third, broader demographic and serostatus data: understanding how the vaccine performs across wider age groups and in populations with different baselines of preexisting dengue immunity will be essential to refine national immunization strategies globally.