The dengue vaccine developed by the Butantan Institute had its effectiveness confirmed in an article published this Wednesday, 31, in the scientific journal New England Journal of Medicine (NEJM), one of the most prestigious in the world. In the publication, the researchers describe that the vaccine was 79.6% effective in preventing the disease, a result that had already been released by Butantan in December 2022, but which now gains greater relevance as it is endorsed by the international scientific community.
This is because, for a study to appear in a high-impact scientific journal, it needs to be reviewed by other researchers to ensure that the data is robust and reliable. “Having an article published in New England It is proof that what we did is relevant and that we followed rigorous data analysis. Peer review is ultra rigorous, they ask about the smallest details”, says infectious disease specialist Esper Kallás, director of the Butantan Institute and main investigator of the study.
The 79.6% efficacy is similar to that of the Qdenga vaccine (80.2%), which will be offered in the SUS from February. The protection index of the Brazilian vaccine was measured by monitoring 16,235 volunteers aged 2 to 59 years for two years. Phase 3 of the study, which began in 2016, will continue until all volunteers complete five years of follow-up, which is expected to happen in June.
After that, the researchers intend to carry out the data analysis stage and prepare the dossier to submit the product registration request to the National Health Surveillance Agency (Anvisa), which should happen later this year, according to Kallas.
“We still have a lot of work to do at home until we finish the complete dossier. Our deadline is the second semester and we have a target of September, but we have to face this with great humility because, sometimes, we need to repeat some analyses, so this target may be mobile, but we are working to try to anticipate”, highlighted the director of Butantan.
Expectations regarding an eventual registration of the institute's vaccine are high because the product has similar efficacy to the Qdenga vaccine, from the Japanese pharmaceutical company Takeda, but with some advantages: it is administered in a single dose and would have a lower cost as it is produced in the national territory. Qdenga, which has just been incorporated into the Unified Health System (SUS) and will begin its application in February to adolescents aged 10 to 14, is given in two doses with an interval of three months between them.
“The great advantage of the single-dose vaccine is that it is capable of inducing rapid immunity, and it is not necessary to wait for the complete vaccination schedule to be completed to obtain the expected level of protection”, explains Kallas.
The arrival of a new vaccine on the market would also help to address another problem: the limited number of doses available. This year, for example, Brazil will receive only 6 million injections from Qdenga, enough to immunize just 3 million Brazilians. Because of this limitation, the Ministry of Health had to restrict vaccination to the age group between 10 and 14 years old and only those who live in cities with a higher incidence of dengue.
In the first four weeks of the year alone, Brazil registered more than 217 thousand cases of dengue, almost five times the number of approximately 45 thousand notifications in the same period last year, according to data from the Ministry of Health.
Asked whether the good results in clinical studies and the challenging epidemiological scenario could lead to an acceleration in the vaccine registration process, Kallás said that dialogue with Anvisa is constant, but that there are still steps to be taken. “Our relationship with Anvisa has been excellent, but we also understand that we have to follow traditional regulatory rites.”
Protection is high in all age groups, study shows
According to data from the Butantan study published in NEJM, protection against the disease was observed in all age groups tested, with 90% in adults aged 18 to 59 years, 77.8% in the group aged 7 to 17 years and 80.1% among children aged 2 to 6 years.
The research results also showed that there was effectiveness both in people who had already had a previous dengue infection and in volunteers without previous exposure to the virus, but the protection rate was higher in the first group (89.2% versus 73.6%) .
The researchers also demonstrated that the vaccine is safe for both groups, unlike the first dengue vaccine licensed in the country, from the pharmaceutical company Sanofi, which is not recommended for people who have never had the infection as it increases the risk of severe manifestations of the disease. .
According to Butantan, the majority of adverse reactions were classified as mild to moderate, the main ones being pain and redness at the injection site, headache and fatigue. Vaccine-related serious adverse events were recorded in less than 0.1% of those vaccinated, and all recovered fully.
The Butantan vaccine was developed against the four serotypes of dengue virus, from the attenuated virus, therefore, it would be able to protect against all of them. However, during the study period, only cases of dengue type 1 and 2, the most prevalent in Brazil, were recorded, which makes it possible to confirm the efficacy of 89.5% for DENV-1 and 69.6% for DENV-1. DENV-2, but it is not yet possible to evaluate the efficacy against the two other serotypes in detail.
Butantan vaccine history
The development of the Butantan dengue vaccine was made possible thanks to the licensing of the technology in 2009 by the National Institutes of Health (NIH), in the USA, which transferred the patents and biological materials relating to the four viral strains that make up the immunizer, thus allowing , that it be produced and distributed in Brazil.
“In 2018, Butantan signed a development and data sharing agreement with the multinational pharmaceutical company MSD, which is working on a similar vaccine, in a joint action to accelerate studies and registration of the product”, detailed the institute, in a note.
Phase 1 of the clinical trial was developed in the United States (2010-2012) by the NIH and phase 2 was conducted in Brazil (2013-2015). The good efficacy and safety results of the first two stages of the studies led to the third phase being carried out by Butantan in 16 Brazilian research centers.