The World Health Organization (WHO) counts 141 candidates for possible vaccines against Covid-19 – 13 of them in the clinical phase, that is, being tested in humans. (read more below)
Brazil, the second country with the most deaths from the disease in absolute numbers, is on the WHO list with two studies in the preclinical phase.
But the country still has other research in preliminary stages in universities and national laboratories, in addition to two important partnerships – one with the University of Oxford and another with the Chinese laboratory Sinovac – for phase 3 in humans, which will test 11 thousand Brazilians .
In the development of vaccines, there is a preclinical phase (with tests on the plate and then on animals) and three stages of the clinical phase (on humans), which cover more people and different methodologies in each step taken (1, 2 and 3) to find the best formulations and periodicities.
The Brazilian participation also includes the only South American doctor invited by WHO to join the International Strategic Group of Experts in Vaccines and Vaccination, a group of studies with 15 experts from around the world that evaluates results found against Covid-19.
Cristiana Toscano is an epidemiologist, professor and researcher at the Federal University of Goiás (UFG) and represents the state in the Brazilian Society of Immunizations (SBIm). She hopes that national participation will stimulate science in Brazil: “It is very promising to have vaccines under development and clinical trials conducted here, we also have professionals participating in various committees around the world. But we could have better internal long-term collaboration strategies that encourage philanthropy. and donations for research funding “, he highlighted.
“The strengthening and investment in research are registered trademarks of the countries that grow the most in GDP and production of products, since they choose to invest in education, science and innovation”, he added.
Although there are good initiatives at the moment, the lack of investments puts Brazil further behind in the vaccine race: “We have technology, people and knowledge, but we don’t have money and we don’t have students, since they cut scholarships. There is no science without This dismantling left Brazilian science broken. It will not have funding for all projects. It is quite possible that some legal idea will die on the beach due to lack of resources “, commented the microbiologist Natalia Pasternak, founder of the Instituto Questão de Ciência.
Oxford Vaccine – Tests in Brazil (phase 3)
One of the most advanced vaccines in the world is that of the University of Oxford, in the United Kingdom, in partnership with the company AstraZeneca, which uses similar principles from studies of vaccines against ebola and Mers (respiratory syndrome of the Middle East caused by another type of coronavirus).
In all, 50,000 people will be tested worldwide – 30,000 in the United States and others in countries in Africa and Asia. In Brazil, 2 thousand volunteers between 18 and 55 years old will be vaccinated. The idea is to announce the results by September and, if all goes well, deliver the vaccines as early as October.
In São Paulo, tests on 1,000 volunteers will be conducted by the Reference Center for Special Immunobiologicals (CRIE) at the Federal University of São Paulo (Unifesp), and count on the financial viability of the Lemann Foundation in all medical infrastructure and equipment.
In Rio de Janeiro, tests on 1,000 volunteers will be carried out by Rede D’Or São Luiz, with R $ 5 million funded by the Network itself, and under the coordination of Instituto D’Or de Pesquisa e Ensino (Idor).
People are recruited from the front line of the fight against Covid-19, in a situation of greater exposure to contamination. They must be seronegative, that is, they have not contracted the disease previously.
The vaccine uses a technology known as a recombinant viral vector. It is produced from a weakened version of an adenovirus that causes a cold in chimpanzees – and that does not cause disease in humans. To this immunizer was added the genetic material used in the production of the “spike” protein of Sars-Cov-2 (the one he uses to invade cells), inducing antibodies.
It is considered a modern and “safe” vaccine because it does not use the virus but a genetic sequence.
Butantan / Sinovac – Tests in Brazil (phase 3)
The Government of São Paulo and the Butantan Institute announced last week a partnership with the Chinese pharmaceutical company Sinovac Biotech, which has already tested in phases 1 and 2 with about a thousand people – having created antibodies in 90% of the patients.
According to the agreement, 9 thousand Brazilian volunteers will be tested and, if the immunization becomes safe, the country will have doses of the vaccine until June 2021. The clinical study will cost R $ 85 million.
The vaccine is called CoronaVac and, as there was control of the pandemic in Asia, the laboratory sought cooperation from countries that still have many people exposed to the virus. Like Brazil.
Experts say it is an “old-fashioned vaccine”, with a technique known since the 1960s, with laboratory manipulation of human cells infected with Sars-Cov-2 itself. The vaccine is produced with inactivated fragments of the coronavirus for introduction into humans. With application, the immune system starts to produce antibodies against the disease-causing agent.
As it works with the entire virus, it requires safe laboratories and good logistics: “It is a technology that Butantan masters. The dengue vaccine is already made like this”, explained Dimas Tadeu, director of Butantan.
The institute is recognized as the largest vaccine factory in Latin America. In 2019, 60 million flu vaccines were provided by Butantan to the federal government.
Incor / FMUSP – (pre-clinical phase)
The national project in the most advanced stage is the one led by scientists from the Faculty of Medicine of the University of São Paulo (USP) and by the Immunology Laboratory of the Instituto do Coração (Incor). The research is funded by the São Paulo State Research Support Foundation (Fapesp).
The group works with a vaccine platform based on virus-like particles (VLP). Tests of three different vaccine formulations are already done in mice.
“When a virus enters our body, the immune system attacks. We don’t want to use the virus, we want to use particles similar to the virus. We did this with chikungunya, Streptococcus and now Covid-19. These particles are just a base that boosts the immune system. In it, we put some pieces of the coronavirus, protein fragments or whole protein, stimulating the immune system to produce antibody ”, explained immunologist Gustavo Cabral, doctor at USP and postdoc at Oxford University and Bern University, Switzerland.
Fiocruz Minas – (pre-clinical phase)
The INCTV (National Institute of Science and Technology in Vaccines), which has a technical basis elaborated by the Viral Diseases Immunology Group of the Oswaldo Cruz-MG Foundation, is currently developing another national alternative. It also has the support of the Butantan Institute.
The researchers built a recombinant virus. The influenza virus (common flu) has been modified inside the laboratory so that it can transport part of the protein from the new coronavirus to the body, offering protection against Covid-19.
“We use the weakened (attenuated) influenza virus as a vaccine vector. We introduced a coronavirus gene that encodes the protein, which is the target of the protective immune response against the coronavirus ”, explains researcher Ricardo Gazzinelli, leader of the Immunopathology Group at Fiocruz Minas and coordinator of INCTV.
The vaccine will begin testing in mice soon. It is thought that it could reach the production phase at the end of 2021, if it finds effectiveness and safety in all tests carried out.
The Institute of Technology in Immunobiologicals (Bio-Manguinhos / Fiocruz) is conducting a synthetic vaccine project. The model is about to be tested on animals (pre-clinical phase). The synthetic form can be faster, cheaper and has stability for storage.
This initiative, however, will not be registered until 2022. The synthetic vaccine is based on B and T cell biomolecules or antigenic peptides, that is, it contains small parts of Sars-CoV-2 virus proteins capable of inducing the production of antibodies.
The biomolecules were produced by chemical synthesis and validated “in vitro” (on the plate). The peptides were coupled in nanoparticles, which act as a form of delivery to activate the immune system. From now on, vaccine formulations will be made with these biomolecules coupled in nanoparticles for evaluation in animals.
“We have to test the conditions on the animals and, if everything goes well, we move on to phase 1 of the clinical test. Otherwise, we have to go back a little bit to improve the design,” said Sotiris Missailidis, deputy director of Technological Development at Bio-Manguinhos.
USP Biomedical Sciences Institute (conceptual phase)
Four surveys are currently taking place at the ICB. Three of them are initiatives of the Vaccine Development Laboratory, coordinated by Luís Carlos de Souza Ferreira, director of the Institute of Biomedical Sciences at USP. They are DNA, RNA and nanoparticle vaccines.
The first two use a genetic sequence of the virus to insert it into the human cell, producing copies of proteins from the Sars-Cov-2 virus. In these models, the virus is not used, only its genetic material (DNA or RNA), which makes the vaccine safer.
As this is a new technology, there are no vaccines of this type on the market yet. There are such initiatives in the United States as well. The company Inovio Pharmaceuticals does tests in phase 1 with the DNA model. Moderna uses RNA and is in phase 2.
“The biggest advantage of working with DNA and RNA is not needing the virus. We only work with genetic sequences, we don’t need to grow the virus, nor do we need security labs. And these platforms are very versatile. With it ready, we can easily switch to genetic sequences of other viruses. For example, if we already had a DNA or RNA vaccine ready and approved for Sars or Mers, it would be quick to adapt it to Covid19 “, analyzed microbiologist Natalia Pasternak.
The ICB nanotechnology model has a pre-clinical phase (in animals) scheduled for September. “We have a platform for assembling nanoparticles that are formed from fragments of the virus. Several vaccines use the proteins of the virus, because it is something safer than using the entire virus, but they sometimes do not induce such a strong response in the body. If these proteins are assembled in a structure that looks like the virus – which is the case with the nanoparticle -, we end up having a stronger response “, said Mariana Favaro, postdoctoral fellow at the ICB Vaccine Development Laboratory, to the USP Journal.
The fourth initiative of the USP Biomedical Sciences Institute also works with nanoparticles and is coordinated by veterinarian Marco Antônio Stephano, from the Faculty of Pharmaceutical Sciences at the University of São Paulo. However, she brings a model of nasal spray vaccine.
This initiative has already been used in mice against hepatitis B.
The spray is applied to the nostrils and has a substance that has a protein from the new coronavirus inside a nanoparticle. The idea is for the organism to produce the IgA Secretoram antibody. Four doses of application will be necessary – two in each nostril, with an interval of 15 days. The prototypes are expected to be ready in September, when animal testing will begin.
Butantan Institute (conceptual phase)
Although betting on the development of Sinovac’s Chinese vaccine, the Butantan Institute also conducts its own research that is seen as a “plan B” in case the vaccines that are in a more advanced stage do not prove to be safe and / or effective. The study is also supported by the São Paulo State Research Support Foundation (Fapesp)
According to Luciana Cezar Cerqueira Leite, a researcher at the Vaccine Development Laboratory, work that has been developed for schistosomiasis can be adapted. “We had very good results, so I redirected the project to use the same platform, but with the coronavirus proteins. There are more advanced vaccine research in the world today using RNA, inactivated virus and adenovirus. We hope that some of them will work and solve the problem. When their results are coming out, we hope to finish the pre-clinical phase of ours, to decide whether or not to follow this plan B “.
In this model, OMVs (external membrane vesicles, in translation) are used as a support matrix for antigens, so that the particle mimics (imitates) the virus. The idea is that particles are released by bacteria to distract the immune system, causing a favorable response against the virus.
“The bacteria releases pieces of its membrane to divert attention from the immune system, which keeps trying to kill these vesicles. It is an escape mechanism for the bacteria. They activate the immune system a lot. They have already been mixing these vesicles with proteins. Now the strategy is stick the virus proteins to its surface, doing something that looks like a viral particle. Against schistosomiasis, this induction produced 100 times more antibodies than the protein alone. And it still activates cells that will attack the virus. , explained the researcher.
Farmacore (conceptual phase)
A biotechnology company in Ribeirão Preto (SP) is studying the production of a vaccine that uses proteins from Sars-Cov-2 itself. This is Farmacore, which works in an exploratory phase (antigen research) and plans to start the pre-clinical phase with mice from July.
The idea is to use pieces of the Spike (S) protein, responsible for the entry of the coronavirus into the cell when it binds to a receptor in human organisms, as well as other proteins and membranes. The goal is to induce neutralizing antibodies that prevent the virus from entering. The carrier system, composed of microparticles, was developed by the American company PDS Biotechnology, a partner in this endeavor.
The next step is to subject the idea to testing in mice, in the pre-clinical phase.