Genetic-based Prediction of Sputnik V Side Effects

Student: Gushhin Aleksandr

Faculty: Faculty of Biology and Biotechnology

Educational Programme: Cellular and Molecular Biotechnologies (Bachelor)

Year of Graduation: 2024

Background/Objectives: COVID-19 vaccination with Sputnik V has been proved to be an effective method to prevent incidence and high severity of SARS-COV2, however, it can cause various side effects based on individual characteristics, including genetic predisposition. Methods: We conducted a GWAS for questionnaire-based difficulties with daily routine after vaccinating with Sputnik V on genetic data of a multi-ethnic group of 20 825 vaccine recepients (7 910 cases, 12 915 controls). All samples were genotyped using Illumina GSA v3 microarray. After that we performed an HLA analysis based on imputed HLA haplotypes. Results: Our study has revaled a strong association between mutations in HLA-DQA1, HLA-DRB1, HLA-B, HLA-DRA, HLA-C genes and reaction to Sputnik V vaccination. We also revealed 14 concise HLA alleles, which increase or decrease risk of feeling unwell after vaccination. Among most significant protective alleles were DRB1*03:01 (OR 0.84, p-value 9.76E-11), DQA1*05:01 (OR 0.83, p-value 2.01E-11) and DQB1*02:01 (OR 0.84, p-value 2.69E-11), which together are known as DR3-DQ2 type, associated with type 1 diabetes and celiac disease. Other protective alleles were В*08:01 (OR 0.82, p-value 4.01E-11), B*07:02 (OR 0.91, p-value 3.14E-5), C*07:01 (OR 0.91, p-value 1.03E-5), C*07:02 (OR 0.91, p-value 5.72E-6). Risk-increasing alleles were DRB1*04:02 (OR 1.24, p-value 1.92E-4), B*44:03 (OR 1.18, p-value 3.74E-5), DQA1*02:01 (OR 1.17, p-value 1.86E-14), DQB1*02:02 (OR 1.17, p-value 6.02E-12), DRB1*07:01 (OR 1.17, p-value 4.99E-14), B*13:02 (OR 1.13, p-value 1.35E-4) and C*06:02 (OR 1.11, p-value 4.47E-6). Conclusion: We performed the first genome-wide association study for adverse reactions to Sputnik V vaccination. Our study reveals the key role of HLA genes in forming variance for individual vaccine-related side effects. Insights on concise HLA-alleles, reducing or increasing risk of adverse reactions, can be integrated into clinical practice to guide personalized vaccine selection.

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