[ad_1]
If everything goes as expected, the Butantan Institute should start in a few weeks, as soon as it receives approval from the health regulatory authorities, human testing of a new compound that is a candidate for a vaccine against Sars-CoV-2: ButanVac.
Developed in collaboration with partners in the United States, the formulation uses a genetically modified, inactivated virus to express the protein. peak of the new coronavirus and thus stimulate an immune response.
The immunizer must be manufactured entirely in São Paulo, using the influenza (flu) vaccine production line and national supplies. “We already have enough batches to start a clinical study, which must be very fast,” said Dimas Covas, director of Butantan, during the announcement of the project, made on the morning of March 26 by the governor of São Paulo, João. Doria, at the institute headquarters.
The authorization request for the phase 1 and 2 clinical trials of ButanVac was sent the same day to the National Health Surveillance Agency (Anvisa), which establishes an average period of 72 hours to respond.
In general, phase 1 assesses if the product is safe, while phase 2 helps to define if it produces any therapeutic benefit, what is its most effective (and safe) dose and if it causes side effects in a sample of people larger than the indicated. it was part of the previous phase.
Also on March 26, Marcos Pontes, head of the Ministry of Science, Technology and Innovations (MCTI), reported at a press conference that, the day before, documentation had been sent to Anvisa for tests on people of another candidate vaccine compound. . : the Versamune-CoV-2FC.
This formulation was developed by the immunologist Celio Lopes da Silva, from the Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), with the São Paulo startup Farmacore and the North American laboratory PDS Biotechnology, and is financed by MCTI (watch Search FAPESP 301).
ButanVac uses so-called viral vector technology to stimulate the immune system to produce antibodies against Sars-CoV-2. A strategy was conceived by the coordinating group of Austro-American virologist Peter Palese, from the Icahn School of Medicine, from the Mount Sinai network of hospitals in New York, in the United States, to generate a cheap product that can be manufactured by countries of average and low income.
Mount Sinai is licensed for the production of this vaccine and transmitted it for free. royalties, through independent agreements, for Butantan, in Brazil, and research centers in Thailand, Vietnam and Mexico.
“We have an agreement with the Butantan Institute to start clinical trials in Brazil using a second generation of the new vaccine. [a ButanVac]. We are also developing vaccines against the Brazilian and South African variants of butantan, ”said Palese. Search FAPESP. According to the virologist, the second generation of the vaccine, which can be kept for three weeks at a temperature of 4 degrees Celsius, is more stable and would elicit an even better immunogenic response. About to be evaluated in clinical trials in Brazil and Mexico, the formulation is in phase 1 trials in people in the United States, Thailand and Vietnam.
In this vaccine platform, a modified form of the Newcastle disease virus, which causes respiratory problems in birds but does not cause serious disease in humans, is genetically modified to incorporate the gene for the protein. peak do Sars-CoV-2.
It is this protein that allows the coronavirus to adhere to and penetrate human cells. The recombinant virus (which contains the coronavirus gene) is then purified and inactivated.
Once inoculated into the body, it is recognized by the cells of the immune system as an external and potentially aggressive agent. The defense cells then initiate the synthesis of antibodies against Newcastle and the protein. peak make coronavirus.
“The vaccine is safe. The Newcastle disease virus has been tested in cancer treatments and there are no reports of significant side effects, ”said Palese, one of the most important researchers in the development of techniques that led to the production of influenza vaccines.
Data from animal studies (preclinical) support the optimism of the virologist. In a first experiment, the Mount Sinai group tested a version made with live attenuated viruses in mice.
According to the results, published in a November 21 article in the magazine EBioMedicine, rodents that received two intramuscular doses of the immunizer produced a large amount of antibodies capable of neutralizing the new coronavirus and, when infected with a version of Sars-CoV-2 that affects rodents, they did not become ill.
In another test, the researchers evaluated the performance of two formulations of the immunizer in mice and hamsters, now with the virus inactivated by a chemical compound (less immunogenic, but safer than the previous one).
One formulation was made with only the inactivated virus, while another also contained an adjuvant, an agent that increases the effectiveness of vaccines by eliciting a more robust immune response. The animals were treated with two doses of the vaccine and then infected with the new coronavirus.
In relation to the control groups that were not immunized, the animals that received the vaccine, especially the version with the adjuvant, showed milder symptoms of the disease, with less weight loss and a much lower amount of virus in the lungs, according to the results. published on December 17 in the Vaccines magazine.
“As with all Covid-19 vaccines, a single dose should offer good protection, but two should provide better and longer-lasting protection,” says Palese.
In partnership with the Mount Sinai group, Palese sent a bank of genetically modified Newcastle disease viruses to Butantan. This bank was replicated by researchers from the São Paulo Institute and used to initiate the production of the immunizing potential.
“We produced a pilot version of an improved version of the immunizer, which makes the protein peak more stable and capable of generating greater immunogenicity, and we sent the inactivated viruses to the Palese group for testing in laboratory animals, ”says biologist Paulo Lee Ho, a Butantan researcher participating in the project. The results would have confirmed the performance of the compound, but have not yet been published.
At a time of vaccine shortage in the world, dominating the production of one or more immunizers is important to the country. And the manufacture of ButanVac, in the beginning, requires almost no investment. It uses a technology very similar to that of the influenza vaccine – manufactured in Brazil by Butantan, which produces around 80 million doses a year for the Unified Health System – and could use the same facilities. Injected into embryonated eggs, the viruses infect the cells of the allantoic fluid and multiply.
They are then isolated, purified, and chemically treated to render them inactive. An egg can generate up to 10 doses of coronavirus vaccine, a yield about 10 times higher than that obtained with the influenza immunizer. According to Covas, after influenza vaccine production was completed, starting in May, Butantan could produce 40 million doses of ButanVac by the end of July. “We can, if all goes well, start using the vaccine in the second half of this year,” Covas said at the March 26 press conference.
Scientific articles
SUN, W. et al. Newcastle disease virus (NDV) expressing the Sars-CoV-2 spike protein as a live virus vaccine candidate. EBioMedicine. Nov 21 2020.
SUN, W. et al. A Newcastle disease virus (NDV) expressing a membrane-anchored spike as a cost-effective inactivated Sars-CoV-2 vaccine. Vaccines. Dec 17 2020.
This text was originally published by Pesquisa FAPESP under the Creative Commons CC-BY-NC-ND license. Read the original here.
