(417c) Predicting the Effects of Sars-Cov-2 Spike Protein Mutations to MHC Class II – Mediated Immune Responses

Starting in 2019, the Coronavirus Disease (COVID-19) pandemic spread rapidly, causing wide-spread disruptions across the world. Over time, numerous variants of concern (VOC) emerged as the causative agent of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), mutated. These mutations all occurred because they provided evolutionary advantages to the virus, but the specific advantages varied. Reasons for mutation include, but are not limited to, increasing infectivity, enhancing survival in the environment, and evasion of immune responses. The focus of this talk is on understanding how SARS-CoV-2 mutations affected immune responses in different ethnic populations.

The adaptive immune response is mediated by the Major Histocompatibility Complex (MHC) proteins, which are coded for by Human Leukocyte Antigen (HLA) genes. The SARS-CoV-2 mutations affect and can disrupt the HLA-driven immune recognition. To understand these effects, we used ProPred to predict the change in binding for every point mutation on the Spike (S) protein of SARS-CoV-2 with respect to the wildtype, providing insight on how mutations increase or decrease viral immunogenicity. Further, HLA alleles appear in different frequencies among ethnic groups. Data from Allele Frequency Net was used to predict how the immune-response altering mutations impacted different ethnic populations.

The most commonly discussed SARS-CoV-2 VOC are the Alpha, Delta, and Omicron strains. Our data show that Delta had more immune response reducing mutations than the other two VOC, which is likely associated with its higher viral load. Alpha, in turn, had mutations that had less impact on the immune response but are known to provide other evolutionary benefits (e.g. increased binding to cellular receptors). Finally, the high number of Omicron mutations helped it evade existing immune responses, from either vaccines or prior infections, but actually increased its overall immunogenicity. This presentation will describe our methods for predicting the immunogenicity impacts of SARS-CoV-2 mutations, provide an overview of the mutations in general, and describe the detailed impacts of their effects on different ethnic populations.