Single-dose dengue vaccine protects 79.6% of vaccinated people, study finds

A single-dose dengue vaccine produced by the Butantan Institute of São Paulo State (Brazil) prevents the development of the disease in 79.6% of vaccinated people, according to an article published in The New England Journal of Medicine.

Called Butantan-DV, the vaccine contains attenuated versions of all four serotypes of the dengue virus. Results from the ongoing Phase 3 trial show it is safe and effective for all age groups between 2 and 59 years old, as well as for people with or without a history of dengue virus infection .

“The publication of the article in the main world medical journal testifies to the rigor and quality of the work carried out by researchers from 16 Brazilian centers located in the five regions of the country and coordinated by the Butantan Institute,” said the Infectious disease specialist Esper Kallás, first author of the article, told the FAPESP Agency. “In June we will complete the five-year follow-up period. Once the data is consolidated, we will know how long the protection induced by the vaccine will last.”

Still according to Kallás, who heads the Butantan Institute, researchers plan to submit a report to ANVISA, Brazil’s health monitoring agency, in the second half of this year to request registration of the vaccine.

“If all goes well, we will get final approval of the vaccine in 2025. We already have the infrastructure to produce it at the Butantan Institute, although it can still be perfected. After all, it is tetravalent, which is four vaccines in one,” he said.

The article published today describes results from the first two years of the Phase 3 clinical trial, which began in February 2016 and involves 16,235 participants in 13 states. Preliminary data disclosed by the Butantan Institute in December 2022 indicated an overall effectiveness of 79.6%. The results for each subgroup evaluated are now detailed.

Vaccine effectiveness was 80.1% for participants aged 2 to 6 years, 77.8% for those aged 7 to 17 years, and 90.0% for the age group 18 to 59 years. Stratification by HIV status showed protection for 73.6% of participants without evidence of prior dengue virus infection and for 89.2% of those previously exposed to the virus. Efficacy was 89.5% against dengue serotype 1 (DENV-1) and 69.6% against serotype 2 (DENV-2).

It was not possible to assess the effectiveness of the vaccine against serotypes 3 and 4 because they were not circulating during the follow-up period. Most adverse side effects were classified as mild or moderate. The main reactions were pain and redness at the injection site, headache and fatigue. Serious vaccine-related adverse events were recorded in less than 0.1% of all people vaccinated, and all recovered.

“The results of phase 2 (the previous clinical trial) showed that the four attenuated viral serotypes of Butantan-DV multiply in the human body and induce a balanced response in terms of antibody production. This leads us to conclude that its effectiveness against DENV-3 and DENV-4 will be equally good,” said virologist Maurício Lacerda Nogueira, one of the trial coordinators.

“It is worth highlighting that the Butantan Institute vaccine has also been shown to be extremely safe for people who have never had dengue fever, which is an advantage over vaccines currently available on the market. is sufficient.” Nogueira is a professor at the Faculty of Medicine of São José do Rio Preto (FAMERP), one of the centers conducting the trials.

To date, two dengue vaccines have been approved in Brazil. One of them is Dengvaxia, produced by Sanofi Pasteur. This vaccine requires three applications and is indicated for people aged 9 to 45 who have had dengue fever. The other is Qdenga, produced by Takeda. Application in Brazil will begin this month, for people aged 4 to 60, regardless of their HIV status. In this case, two doses will be necessary for complete immunization.

The single-dose regimen of Butantan-DV has several advantages, the authors write in the article. In addition to logistical and economic benefits, rapid protection can be important in the event of an outbreak and for non-immune travelers to places where the disease is endemic.

In Brazil, dengue is considered hyperendemic, meaning that its high prevalence remains constant from year to year. According to the Ministry of Health, 1.6 million probable cases were reported in the first 11 months of 2023. So far this year, the number of probable cases has reached 217,841, according to data released Tuesday, January 30 . Fifteen deaths have been confirmed, and 149 are under investigation. Based on these figures, the current incidence rate in Brazil is calculated at 107.1 cases per 100,000 inhabitants and the mortality rate is 0.9%.

Secondary benefits

Development of the tetravalent dengue vaccine began at the Butantan Institute in 2010, using a formulation created by researchers affiliated with the US National Institutes of Health (NIH). Clinical trials in Brazil began in 2013, under the aegis of the project “Development of a tetravalent vaccine against dengue”, led by Neuza Frazatti Gallina, winner of the 2023 Péter Murányi Prize. The phase 3 trial, which should ending in June, could be the largest clinical trial of a vaccine ever conducted solely in Brazil.

“The cost of dengue in Brazil is absurd,” Nogueira said. “The vaccine is expected to reduce mortality and hospitalizations from the disease, which is why the investment of several hundred million reais by the Brazilian government in the development of an indigenous vaccine will have a huge impact on public health.

“Secondary benefits can already be observed. The trial scientists reported in the article conducted clinical trials of CoronaVac during the COVID-19 pandemic. We were therefore prepared. The formation of this research network vaccines is a valuable achievement that the Brazilian government “We must preserve. This will allow us to respond quickly to future challenges of the same type. “