Vaccine development faces lack of investment and advanced laboratories

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If it depends on the national incentive policies in the country, Brazil will continue to be a place for the production of vaccines, but with difficulties in raising itself as a developer of immunization technology —fundamental in the fight against infectious diseases, as was evident in the Covid pandemic .

This is because, according to experts, there are still obstacles to overcome the so-called “Valley of Death” in the production of vaccines and guarantee autonomy.

The first of them occurs in the stage of leaving the concept of proof in the laboratory for people’s arms — that is, getting that molecule tested in the laboratory to be, in fact, effective. This stage has just been won by the SpiN-Tec vaccine, the first 100% Brazilian vaccine against the coronavirus.

Developed by the Federal University of Minas Gerais with support from the Ministry of Science, Technology and Innovation, the vaccine uses a virus protein, the Spike or spicule (molecular hook used by the virus to enter cells) modified to induce the production of antibodies without causing the infection.

In addition to being manufactured at CT Vacinas, a new space for the production of immunobiologicals in Belo Horizonte, the vaccine received approval from Anvisa (National Health Surveillance Agency) to start testing on humans at the end of November.

“This is the first ‘valley of death’, which is starting trials, and we have overcome that. Now there is a second, which is involvement with the private sector to produce vaccines, and this is still lacking in Brazil”, explains the Professor of Biological Sciences at UFMG and coordinator of CT Vacinas, Ricardo Gazzinelli.

According to him, as investment in vaccines is very expensive and high risk, it is more difficult to get support from companies, whether national or foreign. He points out, however, that the phenomenon is not restricted to Brazil and that several vaccines in the world against Covid have failed to advance to testing.

In the country, this is often occupied by the two major vaccine producers in the country, Fiocruz (Bio-Manguinhos, in Rio) and the Butantan Institute, in São Paulo. Together, they are responsible for manufacturing more than 80% of all vaccines used in the PNI (National Immunization Program), but investment in research and development is still low, according to Gazzinelli.

“The two state factories are more involved in production, although they have their research areas. But when you move on to the more advanced clinical stages, with a greater number of participants involved, the cost to reach this stage can go from R$ 10 million to R$ 100 million, and this is where the big pharmaceutical companies come in. In Brazil, there is still no such heavy investment”, he laments.

Luciana Leite, a researcher at the Butantan Institute and director of the Institute’s Vaccine Development Laboratory, says that not always that protein or molecule from the laboratory will have the potential to grow in scale, and that is where a process of trial and error comes in.

“There are a series of processes that need to be carried out by highly qualified teams, process engineers, chemists, biophysicists. And starting this structure from scratch is not easy”, she explains.

Leite has been developing a BCG vaccine from the live organism (pneumococcus) for years. In these cases, another difficulty arises, which is having laboratories with level 3 biosafety.

Clinical analysis laboratories that work with infectious samples are classified from 1 to 4, with 4 being the highest level of safety. According to this classification, biological materials with a high risk of infection need to have a series of steps and physical barriers that prevent contamination of the environment or professionals. Generally, a level 3 is indicated when there is manipulation of live samples of viruses and bacteria, and there is only one classified in the country, at the Institute of Biomedical Sciences at USP. At Butantan, the existing laboratories are level 2.

“It’s not enough just to build a factory, it’s an investment of years. You don’t buy autonomy overnight, you need trained teams, installed infrastructure, regulatory sectors, quality control and other peripherals working”, ponders Leite. “And if demand is low, it’s not worth keeping staff trained, qualified and receiving a salary to make one protein a year.”

According to Gazzinelli, the new center in Belo Horizonte should also be able to make progress in researching a vaccine against leishmaniasis and another against malaria next year. “As we set up a structure and train teams to produce the vaccine against Covid, the expectation is that the next vaccines produced will already have a lower cost”, she says.

For him, if Brazil succeeds in creating its own technology development and research routine, it will be much easier to guarantee autonomy, including to attract investment. “As this happens we will get more resources for the clinical phases [de testagem em humanos]🇧🇷 And there are several diseases that occur around here for which we still don’t have vaccines, and which the pharmaceutical sector is often not interested in seeking. Therefore, this issue of autonomy is fundamental “, he says.


STEP BY STEP TO OBTAIN A VACCINE

Process can take more than a decade

Search preclinical

Research done before testing on humans, animals or cells in the laboratory. It seeks to understand how the pathogen infects the host and possible antigens. It may take several years before this body of knowledge is solid enough.

Clinical research – Phase 1

The test is done with dozens of healthy human beings. The idea is to see if the drug is safe and does not cause side effects. This research phase may take a few months. Many candidates fail at this stage and also at the next stage.

Clinical research – Phase 2

With a few hundred volunteers, they want to know whether the drug, in addition to being safe, has a chance of working. In the case of a vaccine, the idea is that antibodies are generated against the pathogen (it remains to be seen whether they actually immunize)

Clinical research – Phase 3

Based on the safety and possible efficacy results, thousands of people are vaccinated and thousands more receive a placebo (an injection that does not contain the immunizer itself) to quantify the immunization potential of the vaccine candidate

factory building

As a rule, the construction of the factory can take years and only happens after the approval of the vaccine, given that it may prove to be unsafe or ineffective in some of the stages of clinical research, and the work becomes a lost investment

large scale production

Producing a vaccine requires specific equipment and specific techniques. While some vaccines are produced after infecting chicken eggs with viruses, others depend on the production of antigens by microorganisms, for example

Distribution

In addition to guaranteeing the necessary amount to potentially immunize the entire population, it is necessary to have the means for it to reach different countries.

Sources: Diego Moura Tanajura (Federal University of Sergipe), NIH, Harvard University, University of Oxford

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