SARS-CoV-2 Epitope Presentation by Class II HLA Genotypes Common in North American Populations: A Proposed Computational Approach for Vaccine Efficacy Evaluation

Background: Human Leukocyte Antigen (HLA) gene polymorphisms between ethnic groups have been shown to play a role in the heterogeneity of response to SARS-CoV-2, in terms of COVID-19 disease severity and susceptibility, in addition to socioeconomic factors. It was predicted that this finding may extend to vaccine responsiveness. Purpose: To the best of our knowledge, this study was the first that aimed to predict and evaluate the effectiveness of four COVID-19 vaccines across North American ethnic groups, in terms of their ability to trigger CD4+ T cell help, based on class II HLA allele frequencies. Methods: Various databases including the Immune Epitope Database (IEDB) were used in this computational approach. The number of peptide-HLA high-affinity pairs between the most common HLA II haplotypes and SARS-CoV-2 peptides in various vaccine types were retrieved and compared between ethnicities. From this, the efficiency of antigen presentation to CD4+ T cells was evaluated, a crucial component in the context of vaccination for cellular immunity and support in antibody generation. Results: Multiple discrepancies in vaccine effectiveness for ethnic minorities relative to the Caucasian group, overrepresented in vaccine clinical trials, were highlighted. Recommendations were issued in terms of which vaccine types could be most effective for particular ethnicities. Conclusion: There exists a genetic basis for differential responses to vaccines among ethnic groups in North America. However, given the multifactorial nature of vaccine responsiveness and limitations of computational methods, this study offers future research directions to undertake before the findings can be transferred to clinical and public health settings.