As global cases of dengue are already close to last year’s record high of over four million, the Americas region is struggling to contain high transmission levels. Unplanned urbanization, heavier rainfall, warmer temperatures, and the El Nino effect create perfect conditions for the Aedes aegypti mosquito, the primary vector of dengue. 

The Southern Cone region of the Americas, which includes Argentina, Brazil, Chile, Paraguay, and Uruguay, has seen the highest burden of cases and deaths. Brazil alone accounts for close to 3.5 million cases. 

Challenges with vaccine distribution and availability

This year, Brazil became the first country to deploy a newly approved vaccine, Qdenga. The vaccine, manufactured by the Japanese-based pharmaceutical company Takeda Pharmaceuticals, contains weakened versions of all four dengue serotypes. The European Medicines Agency and the UK have approved the vaccine for use in adults and children over four years of age. 

However, the manufacturers can only produce about six million doses – enough for  three million individuals as each person needs two doses.

Currently, Brazil is distributing the vaccine to children between the ages of 10 and 14 in areas of high transmission, and with previous exposure to dengue. This represents only a fraction of Brazil’s population. 

“[T]hey chose this age group because it was based on the analysis of the Minister of Health, the age group that was suffering the highest burden of hospitalization,” explained Dr. André Siqueira, a tropical medicine doctor and clinical researcher in Fundação Oswaldo Cruz, in a recent interview with the One Health Trust.

“We can’t expect that to have a huge effect on the epidemics because it’s a restricted age group and it’s not the whole country. Full immunization is achieved within three months from the initial dose.” 

Given these limitations, the vaccination campaign is controversial in Brazil. “Some people said there’s no point. Even the Minister of Health said it won’t have any impact on this epidemic,” said Siqueira.

However, Siqueira notes that vaccinating this initial cohort creates momentum “of people being involved with dengue to start promoting the vaccination, showing that it is safe and it can have an individual impact.” 

Public support is especially important after a prior vaccine, Dengvaxia, was linked to deaths in children in the Philippines. 

The Sanofi-produced vaccine was mired in controversy after the vaccine was shown to increase the risk of hospitalization for those without prior dengue exposure. When these individuals were infected with dengue, “instead of being protected, they were at higher risk of severe disease.” 

This is due to the dynamics between the four dengue serotypes. The antibodies for one serotype will only protect the individual against future infection from that same serotype. Individuals could then have up to four episodes of dengue over a lifespan. Furthermore, interactions between antibodies from the various serotypes can lead to more severe secondary dengue infection, a process called antibody-dependent enhancement. 

This dengue season in Brazil has seen the circulation of all four dengue serotypes. Many Brazilians are especially vulnerable to DENV-3 and DENV-4 as these subtypes have reappeared this season. 

Vaccine trials for domestically-produced doses

In light of these challenges, researchers in Brazil are in the process of developing a new dengue vaccine to target all four serotypes. The vaccine, from the Butantan Institute in collaboration with the US National Institutes of Health (NIH), shows early promise in clinical trials. The live, attenuated, tetravalent vaccine requires only one dose, unlike Qdenga, which uses a two-dose system with three months between shots. 

In phase 3 trials, the vaccine has shown an efficacy of 79.6% among those without prior dengue exposure, and 89.2% for those with prior exposure. The results, published in The New England Journal of Medicine, are a culmination of years of research and trials, and bolster Brazil’s hopes for disrupting dengue’s hyperendemicity. 

“It should be stressed that Butantan Institute’s vaccine has also proved extremely safe for people who have never had dengue, which is an advantage over the vaccines now available on the market. Furthermore, it can be administered to a broader age group and a single dose is sufficient,”said  virologist Maurício Lacerda Nogueira in a press release. 

Image Credits: PAHO/WHO.