COVID-19: Brazil can become a major vaccine testing laboratory

Two of the most promising vaccines are being tested in the country: one developed by the University of Oxford in cooperation with the British pharmaceutical company AstraZeneca and another by the Chinese company Sinovac

As the COVID-19 pandemic advances and makes new victims daily, the race is accelerating in the world of science that works tirelessly in the search for an effective and safe vaccine against SARS-CoV-2 capable of stopping the escalation of infections. Currently, there are more than 160 vaccines against the new coronavirus under development in the world, of which 27 are already in clinical studies. Here in Brazil, one of the most affected countries in the world, with more than 3.2 million cases and more than 106.500 thousand deaths, by the 15th of August, two of the most promising vaccines are being tested: one developed by the University of Oxford in cooperation with the British pharmaceutical company AstraZeneca and another developed by the Chinese company Sinovac Life Science. The two vaccines have already passed test phases 1 and 2 and are now entering phase 3, when they will be tested on a larger group of people, to see if their effectiveness and safety are confirmed in a larger number of participants. Phase 3 clinical studies for coronavirus vaccines are the first of their kind in the country. The vaccine test developed by the University of Oxford is carried out in partnership with the Federal University of São Paulo (Unifesp) and two other research centers, in Bahia and Rio de Janeiro. The SINOVAC vaccine will be tested in the states of São Paulo, Rio Grande do Sul, Minas Gerais and Paraná, in addition to the Federal District. But will we have an immunizer against the disease this soon? Is it possible that more than one vaccine is effective and approved? And for that, researches around the world are in full swing.

On July 22 the Brazilian Society of Tropical Medicine (BSTM) held a webinar with the participation of Dr. Pedro Folegatti, a Brazilian infectologist and leading clinician in the COVID-19 vaccine program at the Jenner Institute in Oxford, UK and Dr. Ricardo Palacios, medical director of Clinical Research at Instituto Butantan, who coordinates tests with the SINOVAC vaccine in Brazil. Also participating as a debater was Dr. Marta Heloísa Lopes, professor at the Faculty of Medicine of the University of São Paulo (FMUSP), and Dr. Rosana Richtmann, Infectologist at the Emilio Ribas Infectology Institute. Dr. José Angelo Lindoso, an infectious disease specialist at the Emílio Ribas Infectology Institute and professor at the FMUSP infectious disease department, was the moderator of the program.

In his presentation, Dr. Folegatti explained that the Oxford vaccine is developed on a platform that uses an adenovirus as a vector that expresses a SARS-CoV-2 protein surface, produced from a gene that encodes the protein and that was inserted into the adenovirus. “The vector is a non-replicating adenovirus due to the deletion of the gene responsible for this function, causing it not to induce any disease. The gene is replaced by the genes that will encode the proteins that will be immunizing. This process can be used for the development of several vaccines against different diseases. The viral vector is structurally the same regardless of the antigen we want to use”, he added. Also according to the researcher, the advantage of using the vector – simian adenovirus instead of a human adenovirus – is the decrease in the chance of people having neutralizing antibody against the vector that may result in reduced immunogenicity of the vaccine. We need the vector to be infected to express the antigen and from that moment on it can stop replicating, he explained.

Dr. Folegatti also pointed out that the viral vector platform induces not only the humoral but also the cellular response, and that there is some accumulated evidence in recent months showing that cellular immunity may have a more relevant role in protecting against coronavirus in general. Two studies were carried out on non-human primates, two of them with the ferret and one more recent, published in a preprint version, with pigs. The paper is expected to be released in the coming weeks. The researcher pointed out that there is no suitable animal model for evaluating vaccines against SARS-CoV-2, since non-human primates do not get sick like humans and thus it is difficult to transpose the findings. However, the study showed that the vaccine is immunogenic and that it was able to inhibit viral replication in the lower airways. A limitation of the research was that the vaccine did not demonstrate protection against nasal chad.

Dr. Palacios detailed that his candidates route to the vaccine began with the multiplication of the COVID-19 virus in mammalian cells and later the virus is inactivated by a chemical process. In his presentation, the researcher explained that the immune system usually reacts to these preparations with the production of antibodies tailored to the pathogen; and with the amplification of a set of cells that will make more of these antibodies when there is the second dose of vaccination. This is how it happens with the hepatitis A or B vaccine, he exemplified. In May, the journal Science published the results of tests with the vaccine – basically, the multiplied COVID-19 virus itself, purified from the cells in which it grew and properly neutralized, so as not to cause disease – in mice, rats and Rhesus monkeys. For the study, the authors selected 11 strains of SARS-CoV-2. They used one of the strains to inactivate and purify, and used strains from different sources, including European sources, to assess immunogenicity in animals. The mice, rats and monkeys produced antibodies against these strains, an indication that the vaccine could be used against most of the circulating strains.

Dr. Palacios pointed out that, like the Oxford vaccine, SINOVACs vaccine does not have sterilizing immunity. “There is no way to expect, at least for these first generations, sterilizing immunity, although there is a reduction in the amount of viruses that are recovered in the upper areas. And this reduction can have some indirect effect by reducing viral load”, he added. According to him, a vaccinated person will have less chance of transmitting, but it cannot be said that there will be sterilizing immunity as it exists, for example, in the measles vaccine, in which even eradication can be sought. For the researcher, in this case, eradication is not a feasible prospect at the moment. He also recalled that the World Health Organization (WHO) and the American regulatory agency, FDA, recommend that a vaccine that demonstrates at least 50% protection is subject to approval, commercialization and distribution. The good news is that SARS-CoV-2 does not present the pathology paradoxical to the vaccine, that is, a disease enhanced by vaccine.

Dr. Lopes, one of the debaters, in her considerations did not hide her enthusiasm and praised the two promising vaccines investigated in Brazil, a very big differential, according to her. For the professor, the more products, the more chances of containing the pandemic. I believe that other vaccines will probably come to be investigated and this will help to contain the pandemic she said. In her speech, Dr. Lopes echoed a comment published in the journal Lancet, on May 20 by French authors, in which they feared politicization and as a result the hesitation regarding the COVID vaccine in France.

“I am aware that in Brazil, for various reasons, we have witnessed a decrease in vaccination coverage. So, I understand that we should be very careful when introducing discussions about vaccines against COVID-19 in order not to incur politicization, which can even cause hesitation”, she stressed. According to the professor, for this not to happen, it is necessary to promote broad debates, detailed presentations of vaccines, with reliable data, exactly as the Brazilian Society of Tropical Medicine (BSTM) is doing. This is what the population, researchers, public health officials and politicians need she acknowledged. Regarding the Oxford vaccine, Dr. Lopes recommended more robustness in responding to cellular immune analysis. Did she also questioned the SINOVAC doses to be applied: two doses of the vaccine in an interval of 14 days? From a public health campaign standpoint, this is a difficult operation and it needs to be widely discussed with all sectors to avoid polarization and politicization in Brazilian health she noted. Despite the urgent need for a vaccine, Dr. Lopes recalled that we need to be cautious, careful and, in addition, have security and clear data so that it can be made available to the population.

At the beginning of her talk, the medical Infectologist Dr. Richtmann disclosed numbers and talked about the race against the virus and not the race for vaccines. We have 165 vaccines under development, of these, 27 already in trials with humans, in phase 1 2 or 3, and four in phase 3, two of which are here, she quoted. For the doctor, the intense circulation of the virus in the country justifies the choice of Brazil to try a quick response. Following, the infectologist revealed that in the State of São Paulo, from February to June, there were 281.380 confirmed cases of COVID, more than 53 thousand in health professionals, that is, 19% of the confirmed cases in the state affect workers in the Health area. “Nothing is fairer than focusing on them, she said. Another consideration by Dr. Richtmann is about platforms. “We are facing two different platforms, a very new one, with a viral vector, which in practice we do not use. It brings new technologies, which we will have to learn in all aspects, from safety, immunogenicity, cellular immune response. I am convinced that this will make a difference, she said.

The specialist took the opportunity to request agility in the publication of SINOVAC phase 1 and 2 studies, which will collaborate for each one to reach their conclusions. She stressed that those at Oxford recently were published. Finally, the doctor recalled that the SINOVAC vaccine uses a well-known and perhaps the most traditional technology, which is why two doses are needed. “We are in a hurry and that is why I believe that the 14-day interval is correct. If preliminary studies show that there was not much difference between zero-14 / zero-28, I understand, even for the sake of the studys logistics, that it is easier to carry out vaccination in a short time”, she concluded. Finally, she reiterated the need for a great deal of awareness raising of the population about what vaccine efficacy means – it can mean not having the disease; or not having the infection (better in the sense of transmissibility); or not having a serious illness; or have 50% effectiveness. Dr. Richtmann also echoed the expectation raised that the vaccine may be 100% effective, which will not be possible. Our war is against the virus, we seek protection against the disease, and this has nothing to do with politics she concluded.