Pre-clinical trial will identify the formulation and concentration capable of inducing a rapid and lasting immune response, before further development and testing (photo: Léo Ramos Chaves / Pesquisa FAPESP)
Published on 03/23/2021
By Elton Alisson | Agência FAPESP – Researchers at the Heart Institute (INCOR) in the University of São Paulo’s Medical School (FM-USP) in Brazil have begun a pre-clinical trial of potential COVID-19 vaccine formulations.
The aim of the pre-clinical trial is to identify a specific formulation and concentration that induces a rapid and lasting immune response in mice. Once this is achieved, the group can move on to the next steps of the project, which is supported by FAPESP.
“So far we’ve developed three formulations and are testing these in animals, while working on several other formulations in order to pick the best candidate,” Gustavo Cabral, principal investigator for the project, told Agência FAPESP.
The strategy followed for all the formulations is based on virus-like particles (VLPs), which have similar characteristics to viral peptides and proteins such as the spike protein used by the novel coronavirus SARS-CoV-2 to bind to the ACE-2 receptor in human cells and infect them. VLPs are recognized by the immune system but contain no viral genetic material and are non-infectious – hence their potential use in vaccines.
To make sure they trigger an immune response, the VLPs are inoculated together with viral antigens (substances that stimulate the production of antibodies). This approach combines the adjuvant properties of VLPs with the targeting of specific antigens. In addition, Cabral explained, VLPs are safe, natural biological components, which means they can be broken down easily by the organism.
“With this strategy it’s possible to direct the immune system to recognize VLPs conjugated with viral antigens as a threat, and to trigger an immune response effectively and safely,” he said (read more at: agencia.fapesp.br/32761).
The first three vaccine formulations tested in mice are based on peptides that are similar to the viral spike protein and induce antibody secretion by B lymphocytes to prevent the virus from infecting cells.
The researchers are also formulating vaccines based on peptides that stimulate T lymphocytes to kill infected cells and block viral replication.
They also plan to develop formulations based on whole proteins similar to the viral spike protein but that stimulate various types of defense cell, unlike the peptides, which specifically target B or T lymphocytes.
“We’ve had to import the proteins, which we expect to arrive in Brazil this month, but the idea is to synthesize and produce them in our lab, as we’ve already done with the peptides,” Cabral said.
In the pre-clinical trial, the vaccines are injected into the mice at different concentrations. Blood plasma is sampled every week to measure the production of antibodies. The animals’ immune response will be monitored for several months. Eventually the researchers plan to be able to decide which of the formulations and concentrations leads to an acceptable level of immunity to the virus.
“Through continuous monitoring we’ll also find out how many doses of the vaccine will be needed to assure immunity,” Cabral said.
The formulation that performs best in terms of inducing an immune response will be injected into mice that have been genetically engineered to express human ACE-2, the receptor for the SARS-CoV-2 spike protein, in order to see how long they remain immune and make sure the vaccine is safe for testing in humans.
The researchers expect to complete the pre-clinical trial at the end of this year.
“We’re conducting the trial with great care and trying to answer as many questions as possible in order to be ready to make progress with the necessary rigor toward producing a genuinely effective COVID-19 vaccine,” Cabral said.
“In addition to the vaccine, we’re also producing knowledge and a technological platform that can be used to develop vaccines for other diseases, such as zika and chikungunya.”