Coronavirus Data Release: Identification of Novel CD4 and CD8-Stimulating Epitopes From COVID-19

As the worldwide coronavirus situation intensifies, Immunitrack and Intavis (Germany) have joined forces to identify novel candidate CD4 and CD8-stimulating epitopes from COVID-19. This report outlines the rationale for our efforts and includes the dataset as a free download.

COVID-19

The COVID-19 genome encodes 10 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 antibodies¹. Immunisation of animals with S protein-based vaccines has been shown to induce the formation of neutralising antibodies that are effective in preventing infection by homologous coronaviruses.²

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. In recent years, the contribution of cellular responses, particularly those of CD8 T cells, has increasingly been recognised 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.

Better Vaccines with CD4 and CD8-Stimulating Epitopes

When virus entities infect human cells, epitopes from any of that virus’ proteins can theoretically be bound and presented by MHC I receptors on host cell surfaces, leading to stimulation of CD4 and CD8 T cells to provoke antibody-mediated and cellular immune responses (see Figure 1).

At Immunitrack, we 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.

There are a number of epitope prediction algorithms available but these generally only perform well for a subset of Caucasian alleles i.e. these tools are not always reliable for e.g.  MHC-C subtype (HLA-C) and most MHC class II alleles.

Screening COVID-19 Epitopes Against Asian MHC I Alleles

In collaboration with researchers at the University of Copenhagen, we initially used netMHC to make in silico predictions of epitopes presented by 11 MHC I alleles covering approx. 90 % of the Asian population. Using this approach, we compiled a list of 100 candidate epitopes for the following MHC alleles: A*0101, A*0201, A*0301, A*11:01 A*2402, B*40:01, C*01:02, C*04:01, C*0701, C*0702, and DRB1*0401, resulting in 1,100 MHC/peptide binding studies.

For this project we partnered with Intavis, who synthesised the COVID-19 epitopes assessed in this study. Using our unique NeoScreen^® technology we conducted in vitro binding studies of the epitopes. Our study identifies 159 epitopes that stably bind MHC I alleles, and 22 that bind the tested MHC II allele (see report and Table 1).

Download Study Data

We anticipate that this new data will aid stakeholders in identifying which T cell-stimulating epitopes are worth pursuing in a COVID-19 vaccine. We narrowed down the number of epitopes of interest per allele as listed in Table 1.

Download the report containing all stability data obtained for these epitopes.

The stability cutoff was 60 % of a reference peptide. Please consult the report for further explanation.