Butantan prepares to test bird flu vaccine in humans

The Butantan Institute, an agency linked to the São Paulo State Department of Health, will begin testing the first Brazilian vaccine against avian flu (H5N8) on humans. The institute received authorization from the National Health Surveillance Agency (Anvisa) last Tuesday (1st) to begin clinical trials and is now awaiting approval from the National Research Ethics Committee (Conep).

According to Butantan, the monovalent influenza A (H5N8) vaccine will be tested in two doses, with a 21-day interval, in adults aged 18 to 59 years, initially. Afterwards, tests will be carried out on people over 60 years of age.

The institute has completed preclinical studies in mice and rabbits with positive results regarding safety and immunogenicity (ability to generate an immune response). Butantan intends to recruit 700 adult and elderly volunteers, who will participate in phases 1 and 2 of the study in five research centers in Pernambuco, Minas Gerais and São Paulo.

The objective is to finish monitoring these participants in 2026, to have data that covers a wide age range for submitting the registration request to Anvisa.

Risk of new pandemic

The director of the Butantan Institute, Esper Kallás, explains that there are a very large number of avian influenza viruses, and that there is a small percentage of them that can become aggressive and cause more serious diseases. Even though they primarily affect birds, these viruses can reach some mammals that come into contact with them, and eventually, if they adapt, there is a risk of causing infections in humans. According to Kallás, since 1996, a type of avian-specific virus called H5 has demonstrated the ability to be sporadically transmitted to some people.

“In recent years, the virus has been adapting more and more and causing waves of deaths in mammals, first in aquatic mammals, but now also in terrestrial mammals. It is getting closer and closer to having the adaptations it would need to be transmitted between people. This possibility alerts the entire scientific community and public health to the possibility of a pandemic caused by bird flu,” said the director.

According to him, this is not just an opinion of experts from the Butantan Institute in the state of São Paulo or Brazilians. It is an assessment that is present all over the world.

“To anticipate and prepare for this, the Butantan Institute has been working since the beginning of 2023 on developing a candidate vaccine to prevent infection or the development of serious disease from this H5 virus, which has been transmitted mainly among animals in the Americas. Our goal is to verify whether the vaccine is well tolerated, whether it is safe, and whether it induces protection verified by blood tests after people have been vaccinated.”

“If we have this ready, in case this virus starts to be transmitted between people, and causes an outbreak, an epidemic, or a pandemic, Butantan has already taken a development path to produce this vaccine to combat public health,” adds Kallás.

Human-to-human transmission

The medical director of the Butantan Institute, Fernanda Boulos, highlights that the greatest risk for bird flu is inter-human transmission, from person to person.

“If this happens, there is a chance of an epidemic. This has not happened so far because this influenza virus does not have the ability to adapt to the human respiratory system. However, we know that influenza viruses are highly mutagenic and, if they undergo a specific mutation that allows them to adapt to the human respiratory system, then there is a risk of transmission between humans and the risk of an epidemic. We want to anticipate this risk,” said Fernanda.

The director adds that the vaccine under development is an inactivated virus, also called a dead virus, incapable of causing infections. “With the ethical approval of the study being completed, we will open the five research centers that will recruit participants for this study to evaluate whether the vaccine is safe and generated immunity in this first test in humans,” said the researcher.

Lethality

According to Anvisa, experts around the world are warning about the risk of spreading new variants of the avian flu virus, such as H5N1, H5N8 and H7N9, which are noteworthy for their high lethality potential and ability to mutate. Since 2021, these viruses have caused the death of 300 million birds and impacted 315 wild species in 79 countries, according to global data.

“In humans, although they are still rare, the cases are noteworthy due to their severity: between 2003 and 2024, there were 954 infections in 24 countries, with 464 deaths — a fatality rate of 48.6%, significantly higher than that recorded during the Covid-19 pandemic, of less than 1%”, highlights the regulatory agency.

The Ministry of Health reports that, to date, no human cases of avian influenza have been confirmed in Brazil. “The risk of human infection is low and does not occur through the consumption of properly cooked meat or eggs, but rather through direct contact with sick birds or contaminated environments. Therefore, the most effective preventive measure is to avoid contact with dead or sick birds,” the ministry says.

Cases in Rio Grande do Sul

This year, the Ministry of Agriculture and Livestock (MAPA) reported an infection in commercial birds on a farm in the municipality of Montenegro, in Rio Grande do Sul. On June 18, Brazil once again became a country free of avian influenza, after complying with international protocols that provide, among other measures, for a 28-day period without new cases on commercial farms. The official announcement of compliance with the sanitary vacuum period was made by Mapa in a statement sent to the World Organization for Animal Health (WHO).

According to the Ministry of Health, infected birds can spread the virus through saliva, mucous secretions and feces. Infection occurs either through direct contact ─ breathing in the virus contained in droplets or particles carried in the air ─ or through contact with surfaces contaminated by infected birds and then touching their own eyes, mouth or nose.

“People rarely contract avian influenza, but when this occurs, it is usually due to direct unprotected contact with infected birds, without the use of personal protective equipment such as gloves, protective clothing, masks, respirators or eye protection,” says the ministry.

Contingency plan

To ensure a rapid response to possible outbreaks, the ministry launched, in December 2024, the National Health Sector Contingency Plan for Avian Influenza, which guides the ministry's actions, including integrated surveillance, laboratory diagnosis, assistance and health communication.

In addition to the plan, the ministry also published the Guide for Surveillance of Avian Influenza in Humans, with case definitions and other operational details of the entire surveillance routine, from monitoring exposed people to the clinical management of suspected cases and appropriate laboratory flows.

“Brazil is working on different fronts to prepare for the potential risk of human cases. Through the SUS, the Ministry of Health has the capacity to perform laboratory tests, maintains a stock of the drug oseltamivir, used to treat various types of influenza and, if necessary, has the technology to produce vaccines,” it said in a statement.