Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published January 31, 2024


How effective was Butantan–Dengue Vaccine during the 2-year follow-up period?

Kallás et al. recently published a report of the efficacy and safety findings after 2 years of follow-up of an ongoing phase 3 trial in Brazil that is evaluating a single dose of Butantan–Dengue Vaccine for the prevention of symptomatic, virologically confirmed dengue infection in children, adolescents, and adults regardless of their history of dengue exposure. Read the NEJM Original Article here.

Clinical Pearls

Q: What regions of the world have the largest burden of dengue disease?

A: Four serotypes of dengue virus (DENV) circulate worldwide, causing an estimated 390 million infections annually. The largest burden of dengue disease occurs in Southeast Asia and Central and South America. In Brazil, DENV is hyperendemic, with varying incidence across the country. Although most primary DENV infections are asymptomatic or subclinical, DENV can result in severe disease, particularly with secondary heterotypic infection.

Q: What are the limitations of currently available vaccines for dengue?

A: There are currently two licensed tetravalent, live, attenuated dengue vaccines: CYD-TDV, a three-dose dengue vaccine indicated for persons 9 to 45 years of age (an increased risk of severe dengue after CYD-TDV vaccination among persons with no history of dengue infection has been observed) and TAK-003, a two-dose dengue vaccine recently approved in Indonesia for persons 6 to 45 years of age regardless of dengue serostatus. An unmet need remains for a dengue vaccine that offers protection from a single dose across a wide age range, regardless of dengue serostatus. Butantan–Dengue Vaccine is a single-dose, live, attenuated, tetravalent dengue vaccine candidate composed of vaccine viruses representing all four DENV serotypes.

Morning Report Questions

Q: How effective was Butantan–Dengue Vaccine (Butantan-DV) during the initial 2-year follow-up period of this trial?

A: In this trial, a single administration of Butantan-DV was shown to have a favorable safety profile and be efficacious in preventing symptomatic, virologically confirmed dengue caused by DENV-1 and DENV-2. The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) — 73.6% (95% CI, 57.6 to 83.7) among participants who had no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). Cases of DENV-3 and DENV-4 were not observed during the follow-up period, thereby preventing the evaluation of vaccine efficacy against these serotypes.

Q: Might the results of this trial have been affected by the Zika outbreak in Brazil?

A: The absence of cases of DENV-3 and DENV-4 among trial participants corresponds with the lower circulation of these DENV serotypes in Brazil during the trial period. Although numerous DENV serotypes cocirculate and infect a wide range of populations, DENV-1 and DENV-2 may be more commonly associated with disease and (in the case of DENV-2) severe clinical outcomes and are the serotypes against which the vaccine trial showed protection. The effect of preexisting immunity from other flaviviruses (i.e., the viruses that cause Zika and yellow fever) on subsequent DENV infection or Butantan-DV vaccination needs to be explored. The large-scale Zika outbreak in Brazil may have driven lower incidence rates of dengue in 2016 through 2018, shortly after the start of this trial.

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