The Butantan Institute turns 120 this Tuesday, 23, at a time of profound transformation. The development of the Coronavac vaccine during the pandemic placed the entity as a global player in the fight against the coronavirus, according to Butantan’s director of innovation, Ana Marisa Chudzinski-Tavassi.
The expectation now is that the São Paulo institute will stop being just a bibliographic reference in studies on poison and become more recognized by research on immunizers. A new factory should be inaugurated by the end of the year and will enable Butantan to become independent in the development of immunizers, from the preparation of the input to the filling. Today, Coronavac is made in partnership with Sinovac and the antigen, imported from China.
Researcher for 34 years at the institute, Ana Marisa today coordinates an area with 34 other researchers and about 200 employees. To the Estadão, she says that at the moment her attention is all focused on the development of a serum for the treatment of covid-19 patients. The drug proved to be safe in animal testing and should be presented in the coming days to the National Health Surveillance Agency. If approved, clinical trials will begin on infected people.
Read the interview:
When Butantan turned 100, in the commemorative book, then director Hisako Gondo Higashi lamented that the institute’s scientific production had no public or political visibility. Has there been a change in the international level with Coronavac?
Butantan has always been best known in the literature for what it publishes in relation to poison, in animal biology. About the vaccine, it is true that it produced little with bibliographic reference until recently. With the pandemic, a series of much more diverse vaccine-related projects has clearly begun. Butantan is now a new player in the fight against coronavirus. The world started to see Butantan. The last thing that worked on technology transfer was the development of the dengue vaccine, which also served to put Butantan at a different level. Today we use more or less the same technology for the coronavirus, if you look at cell culture, the infection of cells by viruses. It is the same basis. Butantan has expertise, has the infrastructure to produce this, knows how to conduct.
What can be said for people who are suspicious of the Butantan vaccine?
We learned in the pandemic the importance of assembling cohesive teams to seek quick solutions. It was done in record time, but we use management and organization criteria. Butantan has a partnership with Sinovac and is doing what it does routinely … pre-clinical, clinical trials. Nobody skipped steps. Regulatory agencies have also worked briefly. We learned that you can decrease time.
Investment in research, production and development of the vaccine has also increased. Over the 120 years the problem of lack of funding for scientific research at the institute has been recurrent. How is that situation today?
We researchers always turn to funding agencies to run the projects. The development area has been encouraged in recent years to seek public-private partnerships. At Butantan today there are centers of excellence resulting from this partnership. These are long-term projects that seek financing for five years, and then renew for another five. I coordinate the Center for Excellence in New Molecular Targets (CENTD), financed by Fapesp, GSK (pharmaceutical company) and Butantan. In the 1st stage, R $ 22 million was invested. Now there has been renewal for the same amount. It is a basic research, focusing on a subject that the company is interested in, the development of new drugs. The investment is important because it also creates infrastructure with very high performance equipment. It is not just an infrastructure for that project. So much so that within this structure there is also a coronavirus project.
Is there a lack of public investment?
There is this discussion of how to invest. Fapesp is a great partner. Sometimes, there are no big public notices. But now, with the coronavirus, there have been notices. We won a project for the construction of NB3 laboratory (intended for work with microbiological risk agents) to be able to work with viruses with the necessary degree of security. If science starts to propose more centralized discussions, focusing on what it needs for the country, it will be easier to have targeted investment.
What does Butantan lack today?
We lack some structures that leave us uncompetitive. For example, to work with coronavirus, I need this NB3 lab. If I don’t have to be able to do the tests, I stop being competitive, even if we have competence. Before the pandemic started, Butantan had already understood that it should focus on the development of viral vaccines and has focused on that. The research area also has a movement to bring areas together, so that people can work more together and create greater discipline. Today we are divided into buildings and sometimes there is duplication of equipment due to the lack of connection. The board is working to unify.
Will Butantan be able to produce the coronavirus vaccine from start to finish, without having to import input from China?
The input is the antigen, which will be transformed into a vaccine. The NB3 laboratory does this. Butantan has an NB3 laboratory, but is dedicated to the influenza vaccine. You cannot discover one saint to cover another. There is no way to stop the influenza vaccine. During this period, we had two loopholes in which we started to produce the coronavirus antigen for serum production. By the end of the year we will have this new laboratory to help with coronavirus and the development of other vaccines as well.
What about the new factory being built?
Inside this factory, it will be able to produce the input. The vaccine that came through technology transfer means that we only need to have the infrastructure. Butantan is investing to have the entire chain. At the most in one year everything should be ready.
Butantan has been developing a serum that can help treat patients with coronavirus. How is this research?
Everything is ready. This is an example of how good it is to have structure and a group of experts who know the process from beginning to end. 120 years of Butantan, we have been making serum for 120 years. You can do everything, except the vivarium (place where animals are isolated for scientific research). We had to do this in partnership. Unlike Coronavac, which the antigen is from China, here the virus was isolated in the USP laboratory (University of São Paulo) and we used the breach in the influenza NB3 and produced the virus in large quantities. The viruses were inactivated by radiation to be able to circulate in other laboratories without risk. We did a biochemical analysis, characterized the virus, the proteins, whether it was able to produce antibodies, whether they were able to neutralize the active virus. This is all done.
When did this study begin?
We did the process in six months. The last test took longer due to lack of structure. We immunized the horses at the Butantan farm, the plasma of these animals came to the unit of the institute where the processing was done. This product was packaged and analyzed by the quality sector. We did the pre-clinical tests on two species of animal, mouse and rabbit. We saw that the product was safe. We presented to Anvisa in November. Anvisa asked for a challenge test, which is to produce the disease in an animal, treat and see the benefit. We started to collaborate again with USP. But there was a queue to use and develop their projects. We were able to develop the test in early February. And it’s done. The results are very good.
Is serum capable of reducing viral load in a living being?
In a hamster, yes. One day after treatment we saw that it had reduced the viral load in the lungs. From the analysis, we saw that this serum is able to preserve a lot the lung structure and reduce the inflammatory process. This constituted the rest of the document that will be presented to Anvisa. We will schedule a meeting later this week for pre-submission. If you understand that it is ok, we will make the submission, they analyze and decide if we are able to use the clinical trial.
In other words, is there a possibility to solve the disease problem?
Who will say that is the clinical trial. So the need to do it as quickly as possible. The models that we have in animals still can’t say that.
What would be the production capacity of this serum if approved by Anvisa?
The serum you do not need to produce for the world population, only for infected people. We make the serum on a horse. You immunize the horse, draw the blood, the animal does not suffer. You give the antigen, it produces more serum and so on. We started with ten horses, we can buy more. With ten horses, we made about three thousand ampoules. These same horses were re-immunized. Now it is about to fill a new shipment. Once approved, we will shape the production scheme according to the need. You don’t need a factory. The farm is there, there are more horses.