CAJICA, Colombia – Aided by federal funds from the Brazilian government, the University of Sao Paulo is moving forward with developing a precision SARS-CoV-2 vaccine that is about to start preclinical trials.
“I'm trying to avoid taking the route that everybody else is using, even though they are going to be quicker, because I'm trying to do another kind of vaccine,” Jorge Kalil, professor of clinical immunology and allergy at the University of Sao Paulo (USP), who is leading the research team for the SARS-CoV-2 vaccine, told BioWorld. “That is my goal, even if it will be slower.”
Kalil is skeptical about the effectiveness of some of the more than 140 vaccines against COVID-19 in development around the world.
“I'm trying to work, I would say, in what could be a second-generation vaccine,” he said. “Possibly one of the first-generation vaccines will work. I don't know if they are going to work; perhaps they are not, perhaps they will be a complete failure, and if they are complete failure, then our vaccines are in a good position,” Kalil explained.
The approach used by Kalil at the USP aims to discover the relevant B-cell epitopes, responsible for creating neutralizing antibodies. Kalil is also working with T-cell epitopes.
“Although all the vaccinology is based on neutralizing antibodies, I am also a scientist devoted to study the T-cell responses,” he explained. “These are leukocytes in cells, so I decided that I would choose B-cell epitopes and T-cell epitopes and use one of the platforms to present those T-cell and B-cell epitopes,” he said.
To accomplish that task, Kalil collected more than 200 blood samples from infected patients. It wasn´t difficult for Kalil to reach that figure. His son, daughter-in-law and grandchildren became infected, as well as many other relatives and acquaintances. Brazil stands as the country with the second-most COVID-19 cases in the world.
“I used informatics to try and see what might be the previewed epitopes that could be antibody epitopes for neutralization, CD4 epitopes for helper T-cells, CD8 epitopes that would bind to class 1 HLA molecules, to trigger a CD8 cytotoxic T-cell response,” said Kalil.
Kalil´s team is studying the serums and the cells of 210 patients against peptides from the coronavirus’ spike.
“I'm testing peptides from the spike and from the nuclear protein, as well as other proteins that we have, and you can deduce them from algorithms by using informatics, because I wanted to really promote a good T-cell response,” he said.
CD4 T-cell responses are the ones that are helper cells. They help B cells to produce high quantities of antibodies and help the CD8 cytotoxic cells to produce killers.
“CD4 peptides link to the HLA class 2 molecules that we have in our bodies and present this to T cells, and if you have a good T-cell response, then you can provoke the good antibody response,” explained Kalil.
Focus on precision
The Brazilian team is focusing on an exact target, and precision is the key, said Kalil. “The spike is a big protein, so I would like to really provide an exact target and also secondary targets for CD4 T helper cells – these would be many … And for CD8, they recognize a peptide that is presented by the class 1 molecules of HLA, so HLA histocompatibility locus identities, those are the ones that are on the surface of the cell and interact with T cells for both helper and cytotoxicity,” he said.
“I want to make a vaccine that will have these different parts of proteins, and I want to be as precise as I can in directing a response to those,” he explained.
Kalil is still deciding the best model to run the vaccine. An option is to use virus-like particles or other nanostructures that can be swallowed or injected. They can even be nasal.
“I'm going to test all this, and I'm trying to put together a portfolio. I think that perhaps the best way would be to have this vaccine exposed to a mucosal surface, because then you are going to produce many more IgAs. That is one specific type of antibody,” he said.
And while Kalil is using a different approach to those used by scientists across the region in the race for a vaccine, another difference in his project is that he is not concerned about funding, as many are.
The federal government of Brazil is funding the research with $1 million to bring it up to phase I trials. Kalil said he is confident that, once there are results to be shown in that stage, more money will flow in to move the candidate forward to the next phases.
“If I do phase I and I have a good phase I, I'm sure that Brazilian companies, the Brazilian government or international [governments] will join in. Normally you do phase I two ways. That means that you look for toxicity and at the same time you look a little bit if they produce neutralizing antibodies and if they have a T-cell response as well,” he explained.
The University of Sao Paulo and the Brazilian government will hold the rights of the vaccine, with Kalil as its inventor. If they succeed, the forecast is to have a vaccine ready and available by early 2022. Brazil has the biotech companies and infrastructure to scale up production of the vaccine.
“The winner is not the one that arrives first place, [it] is the one that arrives in a better place,” said Kalil. “The best position would be to have a vaccine that will cover over 80% or 90%, ideally 90%, of the population, and also ideally would be a vaccine that could provide good memory.”