A new vaccine against Covid-19 developed in Brazil could 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 obtained permission from Conep (National Research Ethics Committee) to start the clinical trial and are now waiting for the green light from Anvisa (the national health watchdog agency).
We have already delivered to Anvisa all the necessary documents. The answer is expected in the coming weeks. We are ready to start,” said Agência Fapesp Ricardo Tostes Gazzinelli, Coordinator of the Center for Vaccine Technology at UFMG (Federal University of Minas Gerais) and Senior Researcher at Fiocruz (Fundação Oswaldo Cruz).
To develop the vaccine formulation, the group, coordinated by Gazzinelli, combined two different types of Sars-CoV-2 proteins: the N (from the nucleocapsid, the structure that contains the virus’ genetic material) and part of the S (the spike or spike) used by the pathogen.. to adhere to the cell mankind and its conquest.
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.
The Covid-19 vaccines currently in use primarily aim to stimulate the production of neutralizing antibodies against the S protein, which prevents the virus from infecting human cells. This is called the humoral immune response. But, with the emergence of variants with several mutations in the S protein, the antibodies have lost the ability to recognize this antigen. On the other hand, the N protein remained more conserved in the new strains,” explains PhD student Julia Castro, who conducted the preclinical trials 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 (Fundação de Amparo à Pesquisa do Estado de São Paulo). 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 micron 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 either the Wuhan or Delta strain.
Compared to the control group (who received only a placebo), the vaccines had about a tenfold lower viral load and lower 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 are also purity tests – to make sure there are no contaminants in the preparation – and stability tests, which are aimed at detecting the durability of the immune system at different temperatures.
The results show that the vaccine remains viable for up to two weeks when stored at room temperature. However, if it is kept at 4°C, it persists for at least six months.
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 from 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 conducted at the UFMG School of Medicine, coordinated by Professors Helton Santiago and Jorge Pinto.
The proposal 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. Control group volunteers will receive the AstraZeneca vaccine. Then we will compare neutralizing antibody production, total antibody against SARS-CoV-2 virus and T lymphocyte response. Our formulation is expected to stimulate a stronger cellular response,” says Gazzinelli.
The article Promoting neutralization of antibody-independent immunity to wild-type variants and Sars-CoV-2 of interest using the RBD-Nucleocapsid fusion protein can be read at: www.nature.com/articles/s41467-022-32547-y.
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