Human trials of a new COVID-19 vaccine developed in Brazil will begin this year. It performed well in animal tests, reported an article published in August Nature communication. The scientists responsible for the vaccine have recently received permission from the National Health Surveillance Agency (ANVISA) to begin clinical trials.
“There are still some minor adjustments to be made to the study protocol before we once again submit it for approval to the National Council for Research Ethics. [ CONEP ]. We hope to start clinical trials by the end of October,” Ricardo Tostes Gazzinelli, head of the Vaccine Technology Center of the Federal University of Minas Gerais (CTV-UFMG), told Agence FAPESP. Gazzinelli is also a senior researcher at the Osvaldo Cruz Foundation (Fiocruz). Ministry of Health Research Branch.
To develop the vaccine formula, the group led by Gazzinelli combined two different SARS-CoV-2 proteins: the N (for nucleocapsid, which contains the virus’s genetic material) and the S part (for spike, a protein the virus uses to bind to and attack human cells). . The resulting chimeric molecule is called spin. The strategy aims to trigger a cellular immune response that includes the production of immune cells (T lymphocytes) that specialize in recognizing and killing the novel coronavirus. This type of protection should also be effective against novel versions.
“The currently used COVID-19 vaccines are mainly designed to generate neutralizing antibodies against the S protein and prevent the virus from infecting human cells. This is called the humoral immune response. However, with the emergence of variants, many mutations in the S protein, the ability of these antibodies to recognize this antigen is impaired. has been, while the N protein is well conserved in the new strains,” said PhD candidate Julia Castro, who led the preclinical trials with Gazinelli’s supervision.
According to Gazzinelli, also a visiting professor at the University of Ribeirao Preto Medical School (FMRP-USP) in São Paulo, vaccines based on chimeric protein spins do not trigger the production of neutralizing antibodies, but if given as a booster. The shot can stimulate humoral immunity produced by prior vaccination and cellular immunity, providing dual protection.
Challenge Test
The animal tests were performed in a high-biosafety laboratory at the FMRP-USP, thanks to the collaboration with Joao Santana da Silva and Luiz Tadeu Figueiredo, both of whom are also professors there. The research was supported by FAPESP, the Ministry of Science, Technology and Innovation (MCTI) through its Virus Network (Rede Virus), the Minas Gerais Research Funding Foundation (FAPEMIG), and the City of Belo Horizonte (capital of Minas Gerais).
The first step was to test the vaccine’s effectiveness in mice that had been genetically modified to express ACE2, a human protein that the virus uses to infect the host’s cells through its spike (S). This model mimics a severe form of COVID-19.
Some rats were given two doses 21 days apart. Others received a placebo. One month later they were exposed intravenously to a higher viral load. The vaccine protects them against SARS-CoV-2 (isolated in China in 2019), the Delta variant (India, 2020) and the Omicron variant (South Africa, 2021).
In the control group, which was given a placebo, 100% of the animals were infected [ wild-type ] The Wuhan strain or Delta died. Mice exposed to Omicron did not die but developed a significant pathology in the lungs. In the vaccinated group, all animals survived all three types of infection and lung tissue was largely spared. In addition, the viral load was 50 and 100 times lower.”
Julia Castro, PhD candidate
The next step involved testing the vaccine in a moderate disease model. To do this, the scientists used hamsters, which are naturally infected with the virus but not very effectively. They were given two doses of the vaccine and exposed to the Wuhan or Delta strains one month later. Compared to the control group, the vaccinated hamsters had a viral load that was approximately tenfold lower and showed fewer signs of lung damage.
Stability and security
A platform was established to produce chimeric protein spins in genetically modified bacteria at CTV-UFMG. There were also tests to guarantee purity (absence of contaminants in the formulation) and stability (stability at different temperatures).
“The results showed that the vaccine remained viable for two weeks at room temperature and for at least six months when stored at 4 degrees Celsius,” said Gazzinelli, who said safety and toxicity tests were carried out in mice.
According to Gazzinelli, clinical trials are divided into phases I and II. The first phase is expected to vaccinate 80 patients to ensure the vaccine is safe for humans, while the second phase will involve a group of 400 volunteers for vaccine safety testing and evaluation of the vaccine’s immunogenicity – or, in other words, its potency. Induce an effective immune response. The trials will be conducted at UFMG’s medical school and will be led by Helton Santiago and Jorge Pinto, who are both professors there. They plan to vaccinate individuals with any of the available COVID-19 vaccines at least six months in advance.
“This will be a booster shot. The volunteers in the control group will receive the AstraZeneca vaccine. We will then compare the levels of antibodies that neutralize SARS-CoV-2 and T lymphocytes. We expect our formulation to trigger a stronger cellular immune response,” said Gazinelli.