Butantan-DV is the world’s first single-dose dengue vaccine and the first developed entirely in Brazil. The Butantan Institute worked on it for 20 years, using technology licensed from the US National Institutes of Health (NIH). 

Prior to being approved by Brazil’s National Health Regulatory Agency (ANVISA) in December 2025, the vaccine underwent clinical trials with more than 11,000 volunteers monitored for up to five years. The results demonstrated efficacy of 65% against the disease and 80.5% against the most severe cases, according to information from the Butantan Institute.

What was found

From January to May 30, 2026, the pharmacovigilance system (the set of mechanisms that monitors vaccines and medications once they reach the market) recorded 42 reactions not flagged by the studies that led to the vaccine’s approval. 

These episodes included symptoms such as intense abdominal pain, persistent vomiting, and bleeding. Three were classified as severe, and two resulted in death.

The fatal cases involved a 48-year-old woman who developed severe neurological impairment 19 days after vaccination, and a 58-year-old man who developed a severe form of the disease five days after receiving the dose. 

The 42 cases represent 0.008% of the total number vaccinated—a very small proportion, but sufficient to trigger safety protocols. The decision to suspend the vaccine was made jointly by the Ministry of Health and ANVISA, with backing from two technical expert committees.

“This suspension has a purpose,” warned Alexandre Padilha, minister of health, in a statement on Monday, June 8. “First, it is a precautionary measure that should always guide those who respect life and those who respect science,” said Padilha. 

“Second, it allows the Ministry of Health, ANVISA, and the Butantan Institute to further investigate the cases, especially the recorded deaths, for which there is still not sufficient information to establish a causal relationship with the vaccine.”

Those already vaccinated are protected

The authorities clarified that for those who have already been vaccinated, protection is guaranteed. “Those who have already been vaccinated can rest assured. Everyone who has already received the vaccine can count on it—65% protection from contracting the disease five years after administration and 80% protection against developing severe dengue,” said Esper Kallás, an infectious disease specialist and director of the Butantan Institute, in an interview with the GloboNews channel.

Those who received the vaccine less than 21 days ago, however, should watch for symptoms such as fever, intense abdominal pain, persistent vomiting, bleeding, dizziness, or excessive drowsiness. 

The guidance is to seek immediate medical attention should any of these symptoms appear. After 21 days, there is no longer any active component of the vaccine in the body.

The current epidemiological situation is positive: in 2026, until the end of May, Brazil recorded a 94% reduction in the number of dengue cases and a 97% drop in deaths compared with the same period in 2024, according to the Ministry of Health.

Why rigorous testing cannot predict everything

The Butantan vaccine situation illustrates a real limitation of clinical research, not a failure. In an interview with Science Arena published in April 2026, cardiologist and clinical researcher Karla Espírito Santo, of Einstein Hospital Israelita, explained how this process works and why it cannot be shortened.

Before any vaccine or medication reaches the market, it must undergo four phases of testing. In the first, the product is tested on healthy volunteers to verify that it is safe. 

In the second, the appropriate dose and the first signs that it works are assessed. In the third and most extensive phase, thousands of people undergo testing to confirm both efficacy and safety. 

It is only after approval that the fourth phase begins: continuous monitoring of those already using the product in the real world.

The issue is that clinical studies, however rigorous they may be, test a limited number of people. Very rare adverse effects—those that occur in 1 in every 10,000 or 100,000 cases—simply do not appear at that scale. 

They only become visible when the vaccine is used by hundreds of thousands of people at the same time. That is exactly why phase 4 exists.

Without this mechanism, it is impossible to know if an observed effect was caused by the medication or by a preexisting characteristic of the study group.

In the hierarchy of scientific evidence, randomized clinical trials occupy the highest position among individual studies—above them are only systematic reviews and meta-analyses, which combine the results of multiple studies to reach more robust conclusions. 

Isolated case reports sit the base of the pyramid—useful for generating hypotheses, but insufficient to prove that a therapy works.

Espírito Santo also addressed the risks of skipping stages under pressure. Brazil has well-documented examples of this: synthetic phosphoethanolamine, distributed by researchers at the University of São Paulo (USP) without registration with ANVISA, led to thousands of lawsuits filed by cancer patients, despite the lack of evidence of its safety or efficacy. The Supreme Federal Court (STF) declared the law authorizing its use unconstitutional. 

More recently, polylaminin, a protein developed by the Federal University of Rio de Janeiro (UFRJ) to treat spinal cord injuries, also became the target of legal action before completing Phase 1 testing, a stage focused primarily on evaluating safety.

“Even in urgent contexts, such as occurred with COVID-19 vaccines, the necessary studies were conducted before approval,” stated Espírito Santo. “Following this process is a way of protecting the population.” In the case of the Butantan vaccine, this is exactly the process now underway: the system worked by identifying a signal, and science now needs time to understand what it means. 

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