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.
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.