Brazil has 20 Covid vaccine studies underway, but national immunization only comes out in 2023

Brazil has 20 studies of vaccines against Covid-19 in progress, only two of which are in phases 1 and 2 of tests, according to the Ministry of Health. in the SUS (Sistema Único de Saúde) in 2023. However, delays and lack of resources still make national vaccines distant from Brazilians.

This Monday (17), vaccination against the coronavirus completes one year and the capital of São Paulo begins the first phase of immunization of children.

The Ministry of Health says that, between direct hiring and public call (published in April 2020), the ministry has already invested more than BRL 98.5 million in research related to vaccines to combat Covid-19. For researchers, it is little and, therefore, they seek partnerships in the private sector to complete the studies.

The two immunizers that have already entered phases 1 and 2 of testing are Butanvac, developed in São Paulo by the Butantan Institute, and Versamure, developed by the Brazilian biotechnology company Farmacore in partnership with USP (University of São Paulo) in Ribeirão Preto. (SP). Butanvac already has 10 million doses produced to continue the clinical studies.

“At the moment, phase 1 has been concluded, with 320 volunteers. We are finishing the analysis of the phase to be able to request the continuation of the study in the respective ethics committees and at Anvisa. The process suffered a certain delay because the vaccination campaign advanced quickly, so had to make a change in the clinical protocol”, says Dimas Covas, director of the Butantan Institute. The Butanvac study should be around R$ 70 million.

Versamure should start being tested in humans in February, according to Helena Faccioli Lopes, CEO of Farmacore. The study will be carried out with 360 volunteers, in partnership with HCor.

“There was a delay of six months in the United States [chegada de material]. There will be a review process before testing begins, which should take place in February”, says Helena. “We don’t have a date, but we hope to have authorization for emergency use by the end of 2022”, says the CEO of Farmacore.

According to the company, the initial investment by the federal government, exclusively for non-clinical research coordinated by USP in Ribeirão, was approximately R$ 3 million.

“For the phase 1/2 clinical trial, the consortium is seeking resources from the federal government, estimated at R$ 30 million. With everything right, the investment for phase 3, for reasons of a greater number of volunteers and all logistics that this process demands, should be around R$ 300 million”, informs Farmacore, in a note.

Of the immunizers that are still in the pre-clinical phase, one of the bets is the spray that is being developed by USP, which is awaiting approval from Anvisa to begin human trials.

The drug, however, should only be available to the population in 2023. The agency requested a toxicological study from USP, which delayed the process. The university hopes that the next phase of the study can begin in February.

The researchers chose the nasal vaccine because it is the entry of the virus into the human body, acting directly on the mucosa of the nose and airways. “If you manage to block the virus at the gateway, you can have more immunity and even eliminate this infection”, explains Marco Antonio Stephano, professor at the Faculty of Pharmaceutical Sciences at USP.

The cost of the vaccine dose should be around US$ 5 (R$ 27.80 at the current price), but this value still depends on the results of the next tests. The project had a contribution of R$ 4.5 million from the Ministry of Science, Technology and Information in April 2020, but the public notice from the folder still informs release another R$ 30 million. Because of the federal government’s cuts in science, USP is looking for private partners to assist in the study.

Another project that is awaiting the approval of Anvisa for tests with humans is the one being carried out by the State University of Ceará (UECE), in partnership with Fiocruz (Fundação Oswaldo Cruz).

The initiative’s bet is that 2H120 Defense is a low-cost vaccine. According to the researchers, an ampoule with 250 doses can cost around R$11. Because of delays in importing agents, the vaccine should also be available for 2023.

Fiocruz, which already produces AstraZeneca, in partnership with the University of Oxford, is also participating in the development of a subunit vaccine, based on viral proteins, and an RNA vaccine, which creates antibodies.

Both are in the pre-clinical phase. “The goal is to complete the study in 2022 and it should be available to the population in 2023. We depend on some imported inputs, but a good part is produced here”, says Sotiris Missailidis, deputy director of Technological Development at Fiocruz.

Fiocruz’s Institute of Immunobiological Technology (Bio-Manguinhos) was selected by the WHO (World Health Organization) as a center for the development and production of vaccines with messenger RNA technology in Latin America.

“It will be possible to transform Bio-Manguinhos into a Hub for the development, production and transfer of our technology to other countries”, says Missailidis.

The UFMG (Federal University of Minas Gerais) has seven studies of vaccines against Covid-19 – the latest report from the Ministry of Health points to three in the pre-clinical phase. SpiNTec is the most advanced. The institution has already sent Anvisa the request for the application of human tests and is awaiting a response.

According to the university, the stage of clinical trials had resources from the City of Belo Horizonte, which will transfer R$ 30 million, and parliamentary amendments, which guaranteed another R$ 3 million. But it still seeks R$ 300 million for the next phases of the study.

Typically, according to researchers, the study of a vaccine lasts between five and ten years. The situation, however, forced the acceleration of this process.

“What happened with Covid was an acceleration of the possibility of licensing before the end of phase 3 due to the urgency that the pandemic implied. of Immunizations (SBIM).

With the virus still in circulation and the emergence of new variants, according to experts, it is still too early to know whether vaccination against Covid-19 will become an annual application.

Supplies

In addition to the search for money to complete the studies, researchers are trying to find a way to make vaccines less dependent on foreign inputs.

According to Norberto Prestes, president of the Brazilian Pharmaceutical Industry Association, Brazil was already more independent in the 1980s and 1990s, when 50% of the API used was produced in the country. With the opening of the market, this reduced and today the country produces 5%.

“In the last three decades, not only Brazil but also developed countries transferred their production of inputs to Asian countries, in order to reduce their costs. This made China and India massively invest in technology, which made them hegemonies and world powers in the production of pharmaceutical ingredients”, says Prestes.

He understands that for the production of vaccines, Brazil can quickly adapt to the production of inputs. However, for medicines, a large financial investment is needed, something around R$ 2 billion.

On January 7, Anvisa authorized Fiocruz to manufacture an API (active pharmaceutical ingredient) 100% national for the production of vaccines.

In May 2021, the agency had already granted the Good Manufacturing Practices Certification of the new input. Since then, Fiocruz has produced test batches to obtain authorization to use the national API in the vaccine.

Vaccines under development in Brazil

Butantan Institute

– Inactivated Newcastle Disease Virus (NDV) vaccine, which expresses the SARS-CoV-2 protein (ButanVac)*
Development stage: 1/2

– Outer membrane vesicles on multiple antigen platform
Developmental stage: preclinical

– Vaccine based on virus-like particles*
Developmental stage: preclinical

Pharmacore Biotechnology/ Ribeirão Preto School of Medicine

– Recombinant protein-based vaccine**
Development stage: 1/2

Bio-Manguinhos/Fiocruz

– Synthetic vaccine
Development phase: temporarily suspended

– Protein subunit based vaccine
Developmental stage: preclinical

René Rachou Institute (Fiocruz/MG) / National Institute of Science and Technology in Vaccines

– Vaccine based on viral vectors
Developmental stage: preclinical

Heart Institute (Incor) of the USP School of Medicine

– Vaccine based on virus-like particles
Developmental stage: preclinical

Institute of Biomedical Sciences at USP

– Nucleic Acid Vaccine (DNA)*
Developmental stage: preclinical

– Vaccine based on nanoparticles*
Developmental stage: preclinical

– Recombinant protein-based vaccines*
Developmental stage: preclinical

Federal University of Viçosa (MG)

– Recombinant protein-based vaccine*
Developmental stage: preclinical

Faculty of Pharmaceutical Sciences at USP

– Vaccine based on nanoparticles
Developmental stage: preclinical

Federal University of Paraná

– Vaccine based on nanoparticles*
Developmental stage: preclinical

Federal University of Minas Gerais

– Nucleic Acid Vaccine (DNA)*
Developmental stage: preclinical

– Protein chimera based vaccine
Developmental stage: preclinical

Faculty of Animal Science and Food Engineering, USP

– Vaccine based on viral vectors*
Developmental stage: preclinical

Federal University of Rio de Janeiro

– Nucleic Acid (RNA) Vaccine***
Developmental stage: preclinical

Institute of Biophysics of the Federal University of Rio de Janeiro

– Recombinant protein-based vaccine
Developmental stage: preclinical

Laboratory of Biotechnology and Molecular Biology at the State University of Ceará

– Attenuated Avian Infectious Bronchitis Virus Vaccine
Developmental stage: preclinical

* Research projects contemplated with investments from the Ministry of Health and Ministry of Science, Technology and Innovation, through the Public Call
** Project in partnership with international companies/institutions
*** Research project funded by the Ministry of Health

Source: Ministry of Health technical and scientific monitoring report – September/21