SARS-CoV-2 Case Study
The current COVID-19 pandemic, caused by the SARS-CoV-2 virus, has placed an urgent demand on vaccine development, and a number of public and private initiatives are focused on this task. Immunitrack is committed to playing its role in the fight against COVID-19 by applying its technology to support vaccine development and immune monitoring in infected and recovered COVID-19 patients.
Most vaccine development efforts for SARS-CoV-2 focus on targeting the Spike protein, which is present on the viral surface. Several studies concerning influenza viruses as well as hepatitis C virus (HCV) and cytomegalovirus (CMV) have demonstrated that effective viral clearance during viral infection and reduction in symptom severity are dependent on proper CD4 and CD8 T cell activation (1-4). While the CD8 T cell response is important for clearing virally-infected human cells, the presence of CD4 T cells is critical for immune system memory of infection. Thus, we believe that a successful vaccine development strategy against SARS-CoV-2 depends on a strong and lasting activation of both the CD4 and CD8 T cell populations.
Immunitrack is involved in several projects related to SARS-CoV-2 vaccine development and immune monitoring in recovered COVID-19 patients:
Study 1: 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. Click here to read more ▸
Study 2: We are involved in multiple studies analysing CD4 and CD8 T cell populations from people who have recovered from COVID-19. The projects apply ELISPOT as well as flow cytometry using MHC/epitope tetramers specific to stably-binding epitopes identified in Study 1 and from the published report. Here, Immunitrack will produce the peptides and the tetramers that will be applied in the studies. You can read more about these efforts here ▸.
Click here to see a list of links to pages describing our projects related to SARS-CoV-2 vaccine development ▸
Click here to download pdf covering the SARS-CoV-2 Case Study ▸
Study 3: We have performed the most comprehensive HLA restriction study of SARS-CoV-2 Spike-derived epitopes to date. In total, we screened 1,200 9-mers overlapping by 8 amino acids for binding to 9 HLA I and 10 HLA II alleles, and several of these epitopes have been validated independently and reported in peer-reviewed publications. Since T cell responses are likely to differ across ethnicities as a result of the polymorphic nature of HLA I and II receptors, our unique dataset enables a much more in-depth CD4+ and CD8+ T cell study of patient immune responses to SARS-CoV-2 and vaccination, and it may be applied to study how various epitopes may be linked to patient outcomes.
Click here to read more about the study ▸
The results of this study as well as 96 of the SARS-CoV-2 Spike peptides validated in the study are available for purchase here ▸