Researchers at the Immunology Laboratory of the Instituto do Coração (Incor) of the Faculty of Medicine of the University of São Paulo (FM-USP) are developing a vaccine against coronavirus of severe acute respiratory syndrome, Sars-CoV-2.
Through a strategy different from those adopted by pharmaceutical industries and research groups in several countries, Brazilian scientists hope to accelerate development and be able to reach, in the coming months, a candidate for vaccine against the new coronavirus that can be tested on animals.
“We believe that the strategy we are employing to participate in this worldwide effort to develop a vaccine candidate against Covid-19 is very promising and may induce a better immune response than other proposals that have emerged, based primarily on mRNA vaccines. “, I told FAPESP Agency Jorge Kalil, director of the Incor Immunology Laboratory and project coordinator supported through the FAPESP.
Used in the development of the first experimental vaccine against Sars-CoV-2, announced at the end of February in the United States, the technological mRNA platform is based on the insertion in the vaccine of synthetic messenger RNA molecules (mRNA) – which contain the instructions for production of some protein recognizable by the immune system.
The idea is that the immune system recognizes these artificial proteins to later identify and fight the real coronavirus.
The platform that will be used by researchers from the Incor is based on the use of virus-like particles (VLPs) virus like particles).
Multiprotein structures, VLPs have characteristics similar to those of a virus and, therefore, are easily recognized by the cells of the immune system. However, they do not have genetic material from the virus, which makes replication impossible. Therefore, they are safe for vaccine development.
“In general, traditional vaccines, based on attenuated or inactivated viruses, such as influenza[causerof[causadordathe flu], have demonstrated excellent immunogenicity, and the knowledge of their characteristics serves as a parameter for the successful development of new vaccine platforms ”, he said. Gustavo Cabral, researcher responsible for the project.
“But, at this moment, when we are dealing with a little-known virus, for safety reasons it is necessary to avoid inserting genetic material into the human body to avoid adverse events, such as viral multiplication and possibly reversal genetics virulence. For this reason, alternative ways to develop the anti-Covid-19 vaccine must prioritize, in addition to efficiency, safety ”, said Cabral.
In order to allow them to be recognized by the immune system and generate a response against the coronavirus, VLPs are inoculated together with antigens – substances that, when introduced into the human body, cause the immune system to produce antibodies.
Thus, it is possible to combine the adjuvant characteristics of VLPs with the specificity of the antigen. In addition, VLPs, because they are natural and safe biological components, are easily degraded, explained Cabral.
“With this strategy, it is possible to target the immune system to recognize VLPs conjugated to antigens as a threat and trigger the immune response effectively and safely,” he said.
Antigen platform
The researcher did in the last 5 years post-doctorates at the universities of Oxford, England, and Bern, Switzerland, where he developed vaccine candidates using VLPs against diseases, such as that caused by the Zika virus.
Through a project supported by FAPESP, Cabral returned to Brazil where he started a study at the Incor immunology laboratory in early February aimed at developing vaccines against Streptococcus pyogenes – cause of rheumatic fever and chronic rheumatic heart disease – and chikungunya using VLPs.
With the Covid-19 pandemic, the project was redirected to develop a vaccine against the new coronavirus.
“The goal is to develop an antigen delivery platform for cells of the immune system in an extremely easy and fast way that can serve to develop a vaccine not only against Covid-19, but also for other emerging diseases,” said Cabral.
The antigens of the new coronavirus are being produced from the identification of regions of the virus structure that interact with cells and allow it to enter, called proteins spike.
These proteins, which are pointed protuberances around the viral envelope, result in a crown shape that gave this group of viruses the name corona.
After identifying these proteins spike, fragments are extracted from them and conjugated to the VLPs.
Through tests with the blood plasma of patients infected with the new coronavirus it is possible to verify which fragments induce a protective response and, thus, serve as potential candidates for antigens.
“We are already synthesizing these antigens and we are going to test them in the serum of infected patients,” stated Cabral.
After conducting the tests on mice and the vaccine’s effectiveness has been proven, the researchers intend to establish collaborations with other research institutions to accelerate development.
“After verifying that the vaccine neutralizes the virus, we will look for associations in Brazil and abroad to shorten the path and develop as soon as possible a vaccine candidate against Covid-19,” said Kalil.
The researcher is the coordinator of the Immunology Research Institute, headquartered at Incor – one of the INCTs supported by FAPESP in the State of São Paulo.