If in some countries research for a vaccine for the coronavirus advanced, some already in clinical tests, in Brazil the studies are still very preliminary. At least four large Brazilian institutions are working to develop an immunizing agent, but they do so with few resources and are very far from human tests, a crucial phase for the approval of a formula.
The two most advanced initiatives – the Oswaldo Cruz Foundation (Fiocruz) of Minas Gerais and the Immunology Laboratory of the Instituto do Coração (Incor) – have not even reached the stage of so-called pre-clinical tests on animals. They plan to start them in the coming weeks. At the Institute of Biomedical Sciences (ICB) of the University of São Paulo (USP), the work has just passed the conceptual phase, in which the research strategy is decided. The Butantan Institute, in São Paulo, ordered the genetic material for the virus and is awaiting its arrival to begin the study.
CNPq will give R $ 50 million
The resources are modest compared to the billions of dollars spent on research in other countries. The National Council for Scientific and Technological Development (CNPq), for example, opened a public notice for scientific research on Covid-19, be it for diagnosis, treatment or development of vaccines. The projects will compete for R $ 50 million, and research with clinical tests will have a maximum of R $ 8 million each. The result is scheduled for the next 15th.
– We are late and we have little money, unfortunately. Investing in a Brazilian vaccine is strategic for two reasons: national sovereignty and technological independence. There are countries that have already purchased hundreds of thousands of doses before the vaccine is ready. Will there be vaccine for everyone? Will a single dose of this vaccine protect you? And for how long? Doesn’t the same patient have to be vaccinated two or three times a year? – asks Alexandre Machado, from the Viral Diseases Immunology Group at Fiocruz Minas, in front of the laboratory in which 12 researchers, mostly graduate students, are dedicated to developing a vaccine for Covid-19.
Machado’s team is led by Alexandre Gazzinelli, leader of the Immunopathology Group at Fiocruz Minas and coordinator of the National Institute of Science and Technology in Vaccines (INCTV). For now, it has R $ 500 thousand from the Minas Gerais Research Support Foundation (Fapemig) and is awaiting the release of R $ 3.5 million authorized by the Ministry of Science, Technology, Innovations and Communications (MCTIC).
One of the most advanced in the country, Fiocruz de Minas research should start testing in mice in the coming weeks. The platform chosen is that of the vaccine vector – a modified virus, in the case of influenza, is used to transport part of the protein from the new coronavirus, Sars-CoV-2, into the cell. The goal is to develop a bivalent vaccine that protects both influenza and Covid-19. It will not be injectable, but used as an aerosol, nasally.
– The cells of the nasal mucosa have a large amount of this coronavirus receptor. Therefore, we believe that nasal inoculation is ideal, since it is the same route of entry for the virus. It may be more efficient than an intramuscular vaccine to induce local immunity ”explains Gazzinelli.
Clinical tests in 2021
According to the researcher, “with optimism”, animal safety tests will be concluded by the end of the year. Only then, in 2021, will human testing begin. The schedule is similar to the research led by Jorge Kalil, director of the Immunology Laboratory of the Instituto do Coração (Incor), one of the first Brazilian initiatives for a vaccine for Covid-19.
– When the coronavirus arrived in Italy in mid-February, I thought that we had to mobilize the body of researchers to develop a vaccine. I gathered eight of them, in addition to technicians and master’s and doctoral students – says Kalil, who obtained financing of R $ 4.5 million from MCTIC, which has not yet been released.
Kalil relocated resources that already existed in the laboratory to start conceptual studies. He and the Incor researchers opted for the platform known as VLPs, which stands for “virus like particles”, or virus-like particles. Sars-Cov-2 proteins, synthesized in the Incor laboratory, were coupled to the particles, and the material should be tested in mice in the coming weeks. Human tests, only next year.
– If the VLP method does not work, we will move on to other vectors. The key is to study the targets of Sars-CoV-2, in order to understand what is the best way to produce the antibodies – says Kalil. – Usually a vaccine takes ten, 15 years to produce. The fastest was Ebola, in just over five years. People are now talking in months, but it is impossible to do so quickly. On the other hand, I have never seen so many people working for the same vaccine, with so many different platforms.
For Natalia Pasternak, one of the researchers for the Covid-19 vaccine at USP’s Institute of Biomedical Sciences (ICB), “the advantage of having so many different strategies being tested is that one can assume that at least one or two may work”.
– We must remember that we are talking about vaccination for seven billion people. We will not achieve this with a single vaccine formulation – emphasizes Pasternak, who has a postdoctoral degree in Microbiology from USP, is president of the Instituto Questão de Ciência and columnist of the blog A Hora da Ciência, from GLOBO.
Three strategies at USP
Led by Luiz Carlos de Souza Ferreira, director of ICB-USP, the researchers bet on three different strategies, researching DNA, RNA and nanoparticle vaccines. The first two are considered to be the most modern – they use genetic sequences of the virus that are inserted into a vector and introduced into the cell. There are no vaccines on the market, however, that have already been created from DNA or RNA. On the other hand, nanoparticles, when carrying viral proteins, become more like a real virus and are capable of inducing immunity. The forecast is to start testing on animals by the end of this month.
– This is a new virus, with peculiar characteristics and, as there is no clear formulation of the immune response, we decided to use three possibilities. Based on the response of each one, we will choose the way forward. What worries me is the chasm that we will find when we have a chance: how to produce it? And before: how to make human tests feasible? – asks the director of the ICB-USP laboratory, which is requesting resources in the CNPq notice and works, for now, with existing funds and another R $ 200 thousand received from the São Paulo Research Foundation (Fapesp).
At the Butantan Institute, researcher Luciana Cezar Cerqueira Leite, from the Vaccine Development Laboratory, also reallocated resources she already had and obtained another R $ 500,000 from Fapesp to start research on a vaccine for the coronavirus. His group adopts a strategy that was already being tested for schistosomiasis. It uses the so-called bacterial OMV (acronym for “outer membrane vesicles”, or particles of the outer membrane), particles released by bacteria in the body to “distract” the immune system.
– The system tries to kill the vesicles, and the bacteria “escapes”. We are going to use these membranes to carry an amount of virus protein. Thus, they mimic the virus and elicit an immune response – explains Luciana. – Our proposal is very different, it is precisely a plan B in case the other strategies do not work.