Vaccine against Covid-19 developed by groups from UFMG, USP and Fiocruz is ready for human trials

A new vaccine against Covid-19 developed in Brazil could start being tested in humans later this year. The immunizer showed good results in animal studies, which were published this month in the journal Nature Communications. Scientists have already received authorization from the National Research Ethics Commission (Conep) to start the clinical trial and are now awaiting the green light from the National Health Surveillance Agency (Anvisa).

“We have already delivered all the necessary documentation to Anvisa. The answer is expected to come out in the next few weeks. We are ready to start”, tells Agência Fapesp Ricardo Tostes Gazzinelli, coordinator of the Vaccine Technology Center at the Federal University of Minas Gerais (UFMG). ) and senior researcher at the Oswaldo Cruz Foundation (Fiocruz).

To develop the vaccine formulation, the group coordinated by Gazzinelli fused two different SARS-CoV-2 proteins: the N (from the nucleocapsid, the structure that houses the virus’s genetic material) and a portion of the S (spike or Spike) used by the pathogen. to bind and invade the human cell. The resulting chimeric molecule was named SpiN. The strategy aimed to induce the so-called cellular immune response in the body, that is, the production of defense cells (T lymphocytes) specialized in recognizing and killing the new coronavirus. In theory, this type of protection would remain effective even in the face of the emergence of new variants.

“The vaccines for Covid-19 currently in use have the main objective of inducing the production of neutralizing antibodies against the S protein, which prevent the virus from infecting human cells. This is the so-called humoral immune response. variants with many mutations in the S protein, the antibodies lost the ability to recognize this antigen. The N protein, on the other hand, remained more conserved in the new strains”, explains doctoral student Julia Castro, who conducted the pre-clinical tests under the guidance of Gazzinelli .

As explained by the researcher, who is also a visiting professor at the University of São Paulo’s Ribeirão Preto School of Medicine (FMRP-USP), the vaccine based on the chimeric protein SpiN does not, by itself, induce the production of neutralizing antibodies. However, if used as a booster dose, it can stimulate both humoral immunity generated by previous vaccination and cellular immunity, providing double protection.

challenge tests

The experiments with animals were carried out in a laboratory with a high level of biosafety installed at FMRP-USP, thanks to a collaboration with professors João Santana da Silva and Luiz Tadeu Figueiredo. The work was supported by Fapesp. The research also received funds from the Virus Network of the Ministry of Science, Technology and Innovation (MCTI), the City of Belo Horizonte and the Foundation for Research Support of the State of Minas Gerais (Fapemig).

In a first step, the vaccine efficacy was tested in mice genetically modified to express the human protein ACE2, to which the virus attaches (via protein S) to infect the host cell. This model mimics the severe form of COVID-19.

Part of the animals received two doses of the immunizer, with an interval of 21 days, while the others received only placebo. A month later, the rodents were exposed to a high viral load intranasally. Different experiments were carried out to test the protection of the vaccine against the wild strain of SARS-CoV-2 (isolated in China in 2019), against the delta variant (India, 2020) and against the omicron (South Africa, 2021).

“In the placebo group, 100% of the animals infected with the Wuhan strain [China] or with the delta died. On the other hand, mice exposed to the omicron did not die, but developed a significant pathology in the lung. In the immunized group, all animals survived the three strains and lung tissue was much better preserved. In addition, we observed a reduction in viral load that varied between 50 and 100 times”, says Castro.

The next step was to test the vaccine in a moderate disease model. For this, hamsters were used, which are naturally infected by the virus, but not very efficiently. The animals received two doses of the immunizer and, after one month, were exposed to the Wuhan or Delta strain. Compared to the control group [que recebeu apenas placebo]vaccinees had an approximately ten-fold lower viral load and fewer signs of lung damage.

stability and security

At the UFMG’s Vaccine Technology Center, a platform was created to produce the chimeric protein SpiN in cultures of genetically modified bacteria. Purity tests were also carried out there – to ensure that there are no contaminants in the formulation – and stability tests, which aim to discover the durability of the immunizer at different temperatures.

“The results indicate that the vaccine remains viable for up to two weeks when stored at room temperature. If kept at 4 ºC, however, it lasts at least six months”, says Gazzinelli.

Also according to the researcher, the safety and toxicity of the immunizer were tested in experiments with rats. “We already have the clinical batch and we have completed all the tests necessary to obtain approval at Anvisa. That is why we hope to start the clinical trial in mid-September”, he says.

Phase 1 and 2 tests – to assess safety in humans and the ability to induce an immune response – will be carried out at the UFMG School of Medicine, under the coordination of professors Helton Santiago and Jorge Pinto. The proposal is to immunize individuals previously vaccinated against Covid-19 (who have received any of the immunizations available in Brazil for at least six months).

“It will be a booster dose. The volunteers in the control group will receive the AstraZeneca vaccine. Then we will compare the production of neutralizing antibodies, total antibodies against SARS-CoV-2 and the T lymphocyte response. our formulation induces an even stronger cellular response”, says Gazzinelli.