A new COVID-19 vaccine developed in Brazil may begin testing in humans later this year. The immune system has shown good results in animal studies, which are published this month in the journal Nature Communications. The scientists have already secured permission from the National Research Ethics Committee (Conep) to start the clinical trial and are now waiting for the green light from the National Health Surveillance Agency (Anvisa).
says Agência Fapesp Ricardo Tostes Gazzinelli, Coordinator of the Center for Vaccine Technology at the Federal University of Minas Gerais (UFMG) and a senior researcher at the Oswaldo Cruz Foundation (Fiocruz).
To develop the vaccine formulation, the group, coordinated by Gazzinelli, combined two different types of Sars-CoV-2 proteins: N (from the nucleocapsid, the structure that contains the virus’ genetic material) and an S portion (spike or escalate) used by the pathogen to adhere to and invade the human cell. The resulting chimeric molecule was named SpiN.
The strategy aims to trigger a so-called cellular immune response in the body, that is, the production of defense cells (T-lymphocytes) that are specialized in recognizing and killing the new coronavirus. In theory, this type of protection will still be effective even in the face of the emergence of new variants.
“Currently used covid-19 vaccines have a primary goal of stimulating the production of neutralizing antibodies against the S protein, which prevents the virus from infecting human cells. This is called the humoral immune response. Variants with many mutations in the S protein, the antibodies have lost the ability to recognize The N protein, on the other hand, was more conserved in the new strains,” explains doctoral student Julia Castro, who performed preclinical testing under the guidance of Gazzinelli.
As the researcher, who is also a visiting professor at the University of São Paulo Ribeirão Preto School of Medicine (FMRP-USP), explained, the SpiN-based chimeric protein vaccine does not, by itself, induce neutralizing antibody production. However, if used as a booster dose, it can stimulate both humoral immunity generated by prior vaccination and cellular immunity, providing double protection.
The animal experiments were conducted in a laboratory with a high level of biosafety proven by FMRP-USP, thanks to the 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 the first step, the efficacy of the vaccine was tested in mice genetically engineered to express the human protein ACE2, to which the virus binds (via the S protein) to infect the host cell. This model mimics the severe form of COVID-19.
Part of the animals received two doses of the immunizing device, 21 days apart, while the others received only placebo. After a month, the rodents were exposed to a high viral load intranasally. Various experiments have been performed to test vaccine protection against the wild strain of Sars-CoV-2 (isolated in China in 2019), against the delta variant (India, 2020) and against omicron (South Africa, 2021).
“In the placebo group, 100% of the animals were infected with the Wuhan strain [China] Or with Delta Matt. On the other hand, mice exposed to the omicron did not die, but developed significant lung disease. In the immunized group, all animals of the three strains survived and lung tissue was better preserved. In addition, we observed a decrease in viral load of 50 to 100 times,” says Castro.
The next step was to test the vaccine in a mild disease model. For this, a hamster was used, which is infected with the virus naturally, but not very efficiently. The animals received two doses of the immunizing device and after one month they were exposed to the Wuhan or Delta strain. Compared to the control group [que recebeu apenas placebo]The vaccines had about a tenfold lower viral load and fewer signs of lung damage.
stability and security
At the UFMG’s Vaccine Technology Center, a platform for the production of the chimeric protein SpiN in genetically modified bacteria cultures has been established. There have also been tests for purity – to make sure there are no contaminants in the formula – and stability, which are aimed at detecting the durability of the immune system at different temperatures.
“The results indicate that the vaccine remains viable for up to two weeks when stored at room temperature. However, if kept at 4°C, it lasts for at least six months,” says Gazzinelli.
According to the researcher, the safety and toxicity of the immune system was tested in experiments on mice. “We already have the clinical group and have completed all the tests needed to get approval at Anvisa. That’s 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 conducted at the UFMG School of Medicine, coordinated by Professors Helton Santiago and Jorge Pinto. The suggestion is to vaccinate individuals who have previously been vaccinated against covid-19 (who have received any of the vaccinations available in Brazil for at least six months).
“It will be a booster dose. Volunteers in the control group will receive the AstraZeneca vaccine. Then we will compare neutralizing antibody production, total antibodies against Sars-CoV-2 and the response of T lymphocytes. The cellular response,” says Gazzinelli.
Article Enhanced neutralization of antibody-independent immunity to wild-type and SARS-CoV-2 variants using an RBD-Nucleocapsid fusion protein. It can be read at: www.nature.com/articles/s41467-022-32547-y.
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