The University of Copenhagen spin-out company Immunitrack is utilizing its cancer vaccine technology to fight COVID-19.
Since the company was founded five years ago it has developed a novel type of peptide Major Histocompatibility Complex (MHC) assays that looks at the actual stability of the peptide MHC complex.
Sune Justesen, CSO of Immunitrack, explains more about the potential of MHCs for benefiting patients.
“Any adaptive immune response starts with a peptide binding to a MHC creating a peptide MHC complex. Upon binding, the complex is transported to the surface of the cell from where it can bind to a T Cell and initiate an immune response. MHC molecules are polymorphic, meaning that they exist in many versions each binding their special repertoire of peptides. They are inherited from both parents meaning that we all have different MHC molecules and will present different peptides on the surface of our cells. As a population this is good, since it creates a filter that a virus cannot evade by mutation, but it also makes it difficult to study and eventually make peptide based vaccines if you wish to cover a whole population.”
Artificial intelligence have been used to create models that can predict peptide binding to MHC. The most widely used (netMHC) was initiated in 2002 as a response to 9/11 and the bioterror threat that was present at that time, says Justesen.
“It was developed as a collaboration between University of Copenhagen and Center for Biologic sequence at the technical University of Denmark from 2002 to around 2012, in which period I was responsible for the recombinant MHC platform that drove the data generation. The netMHC is still being updated and is as such a fantastic tool research but certainly also has its limitations.”
The S-protein – an attractive therapeutic target
The COVID-19 genome encodes ten proteins, including the “Spike” protein (S-protein), which is a glycoprotein present on the viral surface. The S-protein is considered an attractive therapeutic target given its location, and it is therefore targetable using antibodies.
”Although S-protein may elicit an immune reaction, it is not yet known whether or not this would be sufficient to mount the sustained immune response needed to fight COVID-19 infection,” describes Sune Justesen to NLS. ”In recent years, the contribution of cellular responses, particularly those of CD8 T cells, has increasingly been recognized as an important component of the antiviral immune response. Thus, screening and testing for COVID-19 epitopes that stimulate CD8 and CD4 T cells may aid the development of more effective vaccines. Such efforts could also reveal novel biomarkers to aid immune monitoring in COVID-19-infected persons prior to and after vaccination.”
Sune Justesen and his colleagues believe that the key to developing powerful vaccines is to combine epitopes that stimulate an antibody response with epitopes that stimulate a cellular response. However, finding out which epitopes lead to highly effective immune responses and are thus worth pursuing for vaccine development is a challenge.
”Our first results have confirmed what we already knew, that current in silico epitope prediction tools only works well for a few well described MHC alleles. For the remaining, precision is low, for these alleles the precision could be down to five percent, meaning that out of 100 predicted epitopes only five actually bound to the MHC. We are currently rolling out a new campaign and is going to analyze 1,200 overlapping 9mer (9-bp) peptides from the spike protein. Since most if not all current vaccine efforts are focused on generating immunity to the spike protein we expect this project to be of even higher value,” said Justesen to NLS in the beginning of April.
Photo of Sune Justesen, CSO and Stephan Thorgrimsen, CEO, Immunitrack