Fiocruz develops new vaccines to fight COVID-19

With the start of Oxford/AstraZeneca-Fiocruz production vaccine on national territory, and the batches delivery to the Ministry of Health, this stage is beginning to give its first results to Brazilian society. Still this year, the country will have a vaccine produced entirely in Brazil and already in this first semester the manufacture of the first batches of the active pharmaceutical ingredient (API) will start, which should be available to the population in the second semester. It will be a vaccine 100% produced in Brazil. But Fiocruz continues, in a complementary way, to support the development of other projects leading to new immunizers against COVID-19. The new coronavirus is a major challenge that is possibly here to stay, and as far as the eye can see, many doses of the vaccine will still be needed, not only in 2021 but also beyond. At the moment, Fiocruz is developing six other vaccines, with various national and foreign partners. According to the Foundation's vice-president of Production and Innovation in Health, Marco Aurélio Krieger, mastering the new technological platforms for vaccine development will give Brazil better conditions to face not only the current pandemic but also new public health challenges.

Fiocruz develops six other vaccines with national and foreign partners (photo: Getty Images)

 
The Immunobiological Technology Institute (Bio-Manguinhos/Fiocruz) currently has two internal vaccine projects. "One uses synthetic peptides, based on the S protein sequence, and the other uses a recombinant protein. Both are based on 100% national technology and on the knowledge body we have about the target potentials definition and also the adjuvants use. This new adjuvants generation is present in vaccine formulation and helps a lot in the immune response, potentiating the capacity of the immune response promotion", explains Krieger.

Peptides are small pieces of protein made chemically. In the case of the recombinant protein immunizer, is used a subunit that uses the genetic information from Sars-CoV-2 expressed in another cell, so that we have the functional protein. They are two totally Brazilian projects.

Also at Bio-Manguinhos, there are two partnerships for new vaccine development platforms. According to Krieger, "we already have a vaccine that is efficient and effective, but we need to have new technological platforms that allow us, in an emergency like the one we are experiencing, to get quick answers." One of the platforms is a partnership with a company from Oxford University and that is specific to cellular response.

According to the vice president, "a selection is made of which portions of the virus are recognized by this cellular response and with this a specific vaccine is prepared for this type of response, which can avoid problems that other vaccines may present in the antibodies production that are eventually associated with different situations, as is the case of the dengue vaccine. In the latter case there is a risk of increased infection by the phenomenon known as Antibody Enhanced. "This is a very promising route, which uses the Covid model to incorporate synthetic peptides presented on gold nanoparticles.

Another platform, still with Bio-Manguinhos, is a partnership with the University of Washington in Seattle, the American company HDT and Senai Cimatec, from Bahia. "This is a new generation RNA vaccine, also a very promising platform and analogous to what we do with the T-cell vaccine. The idea is to take advantage of the developing Covid-19 vaccines challenge, and incorporate synthetic vaccine technology, as well as the nanoformulation mechanism to protect the RNA and allow it to enter the cells." This should start phase 1 testing in Brazil soon, in the next two months.

Besides these four from Bio-Manguinhos, there are three other projects. One uses S protein and is the result of a partnership with UFRJ and USP. At Fiocruz, a researcher from the Institute of Science and Technology in Biomodels (ICTB/Fiocruz) is in charge. The project is funded by Inova Fiocruz and seeks to develop a nasal formulation. "The immunizer will be in aerosol form and our expectation is that this nasal spray will stimulate the immune system to induce an IgA response that is extremely important in protecting against respiratory viruses. IgA is the first line of defense against infections in the respiratory tract."

Krieger says that "what differentiates vaccines today, as much as the antigen, is the formulation, which can be specific to activate yet another type of response. We have oral vaccines, intramuscular vaccines, and new applications have emerged. Nasals can develop a very strong response to Sars-CoV-2. It would be more effective and easier to use, as well as having the ability to promote antibodies before the virus enters."

There is an initiative being led by the René Rachou Institute (IRR/Fiocruz Minas Gerais), which in partnership with UFMG and the support of the Ministry of Science and Technology has created a vaccine technology center. It is a viral vector-based vaccine, like the Oxford vaccine, although with a different vector. "All of these vaccines are past proof of concept and are completing pre-clinical trials to enter the clinical phases. The two with external partnerships are already in the clinical phase outside Brazil.

These immunizers could be available by the second half of 2022. "It takes time to do all the clinical trials, prepare materials to produce, the cell lots, virus lots, the certificates, etc. Synthetics have a faster process, but there may be a need to validate that formulation and prepare inputs." Normally this process would take a year and a half, with two validation batches and three consistency batches, with 100 days to make each batch, but with the emergency we managed to reduce this time to six months.

"These new projects, at a technological revolution time in this field, will lead us to master new platforms, new adjuvants, and new ways of application. A technological domain that can be used in other situations that arise," Krieger points out.

The vice-president stresses that "Brazil needs to have this technological mastery, which will give the country a much greater response capacity. Brazil has a privileged situation because it has large national producers, such as Butantan and Fiocruz, which are managing to deliver vaccines to the population. Few countries in the world have more than 10 million people vaccinated. And we succeeded, because of these two public producers. We are fast approaching the conclusion of the works at Bio-Manguinhos, which will increase our autonomy. In April there will be a visit from Anvisa and we hope to receive the certificate to start API production in May for our registered vaccine."

All this technological advance, allowing us to face new challenges, such as the frightening COVID-19 pandemic, leads Krieger to point out that "we will be better prepared for the old problems that persist, such as arboviroses, malaria, leishmaniasis, schistosomiasis, and all the other neglected diseases that continue to cause illness and death. We will have more tools for the new and also for the old challenges. Now we are looking for a vaccine for the pandemic worst moment, aiming to decrease the population viral load, but soon we will return to the search for immunizers for other diseases.”