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The researchers from the Butantan Institute will combine innovative biotechnology techniques to formulate a new vaccine against covid-19. The goal is to more effectively induce different types of immune responses against the new coronavirus (SARS-CoV-2) in the body.
The new strategy is inspired by a mechanism used by certain bacteria to “outwit” our immune system: they release tiny spheres made from the material in their membranes as bait to deflect the body’s defense. These vesicles, called membranes by researchers, have the property of intensely activating the immune system and, therefore, attract cells and defense molecules in the body.
The researchers will take advantage of this device from the membrane vesicles and bind surface proteins from the new coronavirus. Created in the laboratory, these vesicles would attract the immune defense against the surface proteins of SARS-CoV-2, inducing a memory to mobilize in case of an eventual infection. The formulation would stimulate not only the production of antibodies, but also other cells linked to the immune system, such as macrophages and white blood cells.
“For this approach, we brought together two different strategies that we have already been using in developing vaccines against other diseases. The new technique allows the formulations to contain a large amount of one or more virus antigens in a strongly adjuvant platform, inducing a more pronounced immune response, “says Luciana Cezar Cerqueira Leite, researcher at the Vaccine Development Laboratory at the Butantan Institute .
The study, supported by FAPESP, integrates a research platform that involves the development of vaccines against whooping cough, pneumonia, tuberculosis and schistosomiasis, based on techniques developed for recombinant BCG (used to prevent severe forms of tuberculosis in children. ). Recently, a new line was created in the project to develop a vaccine for covid-19.
“All over the world, and also here in Brazil, different techniques are being tested. Many of them build on what was already being developed for other viruses, such as the one that caused the SARS outbreak in 2001. We hope they work, but the fact is, no one knows if they will really protect. In this time of pandemic, it is not too much to try different strategies. Our approach will take longer to come out, but if the ones being tested don’t work, we already have plans B, C or D ”, says the researcher.
Many vaccines consist of solutions with the killed or attenuated pathogen. These are called cellular vaccines that, when injected into the individual, aim to develop the immune response against the microorganism, such as specific antibodies and other defense cells safely, without suffering the consequences of the disease. In this way, the individual is immunized, having a “combat memory” of the immune system against a specific pathogen.
“Cellular vaccines are simple and often effective ways to obtain an immunizer, however, these approaches do not always work, especially for pathogens with high antigenic variability or more complex organisms, with more sophisticated mechanisms to avoid the immune system,” says the investigator.
Combined strategies
The Butantan group proposes the combination of two strategies for the development of an acellular vaccine. On the one hand, there are the recombinant surface antigen proteins of the new coronavirus, which have the role of triggering the production of specific antibodies against SARS-CoV-2. On the other hand, outer membrane vesicles (outer membrane vesicles known as OMVs) are used as a support matrix for antigens, so that the particle mimics the virus.
“The vesicles of the outer membrane can modulate the immune response, in general, increasing and improving protection. Many vaccines have aluminum hydroxide as their main adjuvant. In our case, we will use OMV to present the antigen with a strong built-in adjuvant power, which guarantees a better response, “he says.
For this, the vaccine in development in Butantan will use an innovative antigen presentation platform called the Multiple Antigen Presentation System (MAPS), developed by a collaborator from Harvard University (United States) and used in an experimental formulation against pneumococcus. .
Basically, the molecular complex is assembled by a coupling system similar to that used for detection in the ELISA reaction (enzyme-linked immunosorbent assay), widely used in diagnostics. This type of laboratory test is used to detect antibodies against a certain pathogen and therefore diagnose the disease. In the process developed at Harvard, one or more antigens bind to the polysaccharides in the bacteria’s capsules, as if they were suitable pieces.
“It is a platform that allows the non-covalent binding of proteins in a very efficient way, allowing saturating the surface of the OMV with viral proteins, making them very immunogenic,” Cerqueira Leite told Agência FAPESP.
The idea of using OMV arose from observing a strategy that certain gram-negative bacteria adopt to escape the host defense system. “When they infect organisms, bacteria produce these vesicles from their own outer membrane. The goal is to disrupt the immune system response. Antibodies and other cells related to the immune system are trying to kill the vesicles instead of attacking the bacteria, which are free to multiply in the body, “he says.
In the new formulation, the presence of these extracellular vesicles has the function of stimulating the immune response. “They are very immunogenic. Recent studies show that they have a great capacity to activate dendritic cells and macrophages, “he says.
SOURCE: Maria Fernanda Ziegler | FAPESP Agency
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