Brazilian scientists are developing a vaccine against the new coronavirus
March 18, 2020
By Elton Alisson | Agência FAPESP – Researchers in São Paulo, Brazil, are developing a vaccine against SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19.
The researchers are affiliated with the Immunology Laboratory of the Heart Institute (INCOR), part of the University of São Paulo’s Medical School (FM-USP).
By pursuing a different strategy from those of the pharmaceutical companies and research groups in other countries, the Brazilian scientists concerned hope to speed up the development of a candidate vaccine against the new coronavirus for testing in animals within the next few months.
“We believe the strategy we’re pursuing to participate in this global effort to develop a candidate vaccine against COVID-19 is highly promising and could induce a better immune response than the other vaccines that have been proposed, based essentially on mRNA,” Jorge Kalil, head of the laboratory, told Agência FAPESP.
Kalil is Professor of Clinical Immunology and Allergy at FM-USP and co-principal investigator for the project, which is supported by FAPESP.
The mRNA technological platform was used to develop the first experimental vaccine against SARS-Cov-2, announced at the end of February in the United States. It is based on the insertion into the vaccine of synthetic messenger RNA molecules containing instructions to produce proteins recognizable by the immune system.
Having recognized these artificial proteins, the immune system should then be able to identify and combat the new coronavirus.
The platform that will be used by the researchers at INCOR, however, is based on the use of virus-like particles (VLPs).
VLPs are multiprotein structures that mimic the organization and conformation of authentic native viruses so that they can easily be recognized by immune system cells, but they contain no viral genetic material, cannot replicate, and are safe for use in developing vaccines.
“Conventional vaccines based on attenuated or inactivated viruses, such as influenza, have generally proved excellent in terms of immunogenicity [provoking an immune response], and knowledge of their characteristics serves as a parameter for the successful development of new vaccine platforms,” said Gustavo Cabral, the other co-principal investigator for the project.
“Right now, however, we’re dealing with an unknown virus, and introducing its genetic material into the human organism would be unsafe: it could have adverse effects such as viral multiplication and possibly reversion to virulence via genetic mutation. For this reason, alternative approaches to the development of a COVID-19 vaccine must prioritize safety as well as efficacy.”
To make sure they are recognized by the immune system and trigger a response against viruses, VLPs are inoculated together with antigens (substances that stimulate the immune system to produce antibodies). In this way it is possible to combine the adjuvant properties of VLPs with the targeting of specific antigens.
In addition, Cabral explained, VLPs are easily broken down by the organism and safe because they are natural biological components.
“With this strategy it’s possible to direct the immune system to recognize VLPs conjugated with antigens as a threat, and to trigger an immune response effectively and safely,” he said.
In the past five years Cabral has conducted postdoctoral research at the University of Oxford in the United Kingdom and the University of Bern in Switzerland, developing candidate VLP vaccines against zika and other viruses.
After returning to Brazil, Cabral began working at INCOR on the aforementioned project funded by FAPESP, initially aiming to develop VLP vaccines against Streptococcus pyogenes, the bacterium that causes acute rheumatic fever and rheumatic heart disease, and against chikungunya virus.
In response to the COVID-19 pandemic the project has been redirected to the development of a vaccine against the new coronavirus.
The project also featured participation from Edécio Cunha Neto, a professor at INCOR who performs research at the institute’s Immunology Laboratory. Cunha Neto took part in the decision-making concerning Cabral’s project approach on COVID-19, as well as in designing the experimental vaccine.
“The goal is to develop a platform that delivers antigens to immune system cells in a highly simple and rapid manner, and that can be used for vaccines against other emerging diseases as well as COVID-19,” Cabral said.
Production of antigens of the new coronavirus must begin with the identification of its spike protein, the major surface protein it uses to interact with and penetrate human cells.
Spike proteins are needle-like protuberances that form a ring around the viral envelope. This configuration may explain the virus’s name, as the Latin word “corona” means crown.
Once the spike proteins are identified, fragments of them are extracted and conjugated with VLPs.
By means of tests with blood plasma from patients infected by the new coronavirus, it is possible to find out which fragments induce a protective response and may therefore serve as candidate antigens.
“We’re now synthesizing these antigens and will test them in serum from infected patients,” Cabral said.
The candidate vaccine will have to be tested in mice to prove that it is effective. The researchers then plan to collaborate with colleagues in other centers to accelerate its development.
“Once we’ve demonstrated that the candidate vaccine neutralizes the virus, we’ll join forces with other scientists in Brazil and elsewhere to develop the COVID-19 vaccine with all possible speed,” Kalil said.
Kalil heads the Institute for Research in Immunology, hosted at INCOR and one of the National Science and Technology Institutes (INCTs) supported by FAPESP in the state of São Paulo and the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government.
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