A phase 3 trial published in the New England Journal of Medicine (NEJM) has shown promising results for the single-dose tetravalent Butantan-Dengue Vaccine (Butantan D-V). The vaccine demonstrated an impressive 80% protection rate among participants with no prior exposure to dengue and an even higher protection rate of 89% among those previously exposed to the disease.
This groundbreaking vaccine is the product of painstaking research undertaken by Brazil's Butantan Institute. The study, which included data from 16 Brazilian centers spanning all five regions of the country, comes at a crucial time when approximately one million Brazilians contract dengue annually. With an incidence rate calculated at 107.1 cases per 100,000 inhabitants and a fatality rate standing at 0.9%, there is little doubt that these findings are highly significant.
The lead author of this study, Esper Kallas, PhD, revealed that they will complete their five-year follow-up period in June this year. Once consolidated data becomes available, researchers can determine how long-lasting the protective effects induced by the vaccine are likely to be. If everything goes according to plan, final approval for this revolutionary vaccine could be granted as early as 2025.
Commenced in February of 2016, the phase-3 trial involved over sixteen thousand participants across Brazil; about ten thousand received vaccinations, while around six thousand were administered placebos.
When examining two-year vaccine efficacy (VE), figures stood at an encouraging figure of nearly eighty percent among individuals lacking evidence of previous dengue exposure and just under ninety percent amongst those who had been exposed before.
In terms of overall efficacy against type-1 dengue infection, rates averaged between mid-eighties and high-nineties depending on whether subjects had previous seropositive or seronegative status, respectively; similarly moderate numbers were recorded against type-2 dengue infections. Unfortunately, due to lack of circulation during the study period, no data was obtained regarding efficacy against dengue serotypes 3 and 4.
Mauricio Lacerda Nogueira, PhD, emphasized that the Butantan Institute's vaccine has proven incredibly safe even for individuals who have never previously contracted dengue—a significant advantage over other vaccines presently available on the market.
Notwithstanding these promising results, Scott Halstead, MD, suggests in his commentary that trials for Butantan D-V should continue given its potential for a large-scale impact on global health.
Existing vaccines such as Dengvaxia (requiring three doses) and TAK-003 (requiring two doses) have their own limitations; while Dengvaxia is recommended only to people aged between nine and forty-five with at least one documented case of dengue infection, TAK-003 showed an increased risk of hospitalization among vaccinated seronegative participants.
Halstead also highlighted how the Zika virus’s introduction into Brazil since 2015 has altered natural infection patterns, with Zika acting as a priming force in the immune system against dengue infection, thereby eliminating the circulation of serotypes 3 and 4 post-2016.
In conclusion, he observed: "Given the realities of the dimensions of the dengue pandemic, a highly effective, one-dose tetravalent vaccine remains in high demand." The continuation and possible expansion of clinical trials could be instrumental in addressing this need.