Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects
COVID-19 vaccines have been instrumental tools in reducing the impact of SARS-CoV-2 infections around the world by preventing 80% to 90% of hospitalizations and deaths from reinfection, in addition to preventing 40% to 65% of symptomatic illnesses. However, the simultaneous large-scale vaccination o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/7/743 |
| _version_ | 1797444539584086016 |
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| author | Rima Hajjo Dima A. Sabbah Alexander Tropsha |
| author_facet | Rima Hajjo Dima A. Sabbah Alexander Tropsha |
| author_sort | Rima Hajjo |
| collection | DOAJ |
| description | COVID-19 vaccines have been instrumental tools in reducing the impact of SARS-CoV-2 infections around the world by preventing 80% to 90% of hospitalizations and deaths from reinfection, in addition to preventing 40% to 65% of symptomatic illnesses. However, the simultaneous large-scale vaccination of the global population will indubitably unveil heterogeneity in immune responses as well as in the propensity to developing post-vaccine adverse events, especially in vulnerable individuals. Herein, we applied a systems biology workflow, integrating vaccine transcriptional signatures with chemogenomics, to study the pharmacological effects of mRNA vaccines. First, we derived transcriptional signatures and predicted their biological effects using pathway enrichment and network approaches. Second, we queried the Connectivity Map (CMap) to prioritize adverse events hypotheses. Finally, we accepted higher-confidence hypotheses that have been predicted by independent approaches. Our results reveal that the mRNA-based BNT162b2 vaccine affects immune response pathways related to interferon and cytokine signaling, which should lead to vaccine success, but may also result in some adverse events. Our results emphasize the effects of BNT162b2 on calcium homeostasis, which could be contributing to some frequently encountered adverse events related to mRNA vaccines. Notably, cardiac side effects were signaled in the CMap query results. In summary, our approach has identified mechanisms underlying both the expected protective effects of vaccination as well as possible post-vaccine adverse effects. Our study illustrates the power of systems biology approaches in improving our understanding of the comprehensive biological response to vaccination against COVID-19. |
| first_indexed | 2024-03-09T13:13:39Z |
| format | Article |
| id | doaj.art-e8478bfc22cb4f3e98fba621d14d960b |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T13:13:39Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-e8478bfc22cb4f3e98fba621d14d960b2023-11-30T21:39:04ZengMDPI AGPathogens2076-08172022-06-0111774310.3390/pathogens11070743Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side EffectsRima Hajjo0Dima A. Sabbah1Alexander Tropsha2Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanLaboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USACOVID-19 vaccines have been instrumental tools in reducing the impact of SARS-CoV-2 infections around the world by preventing 80% to 90% of hospitalizations and deaths from reinfection, in addition to preventing 40% to 65% of symptomatic illnesses. However, the simultaneous large-scale vaccination of the global population will indubitably unveil heterogeneity in immune responses as well as in the propensity to developing post-vaccine adverse events, especially in vulnerable individuals. Herein, we applied a systems biology workflow, integrating vaccine transcriptional signatures with chemogenomics, to study the pharmacological effects of mRNA vaccines. First, we derived transcriptional signatures and predicted their biological effects using pathway enrichment and network approaches. Second, we queried the Connectivity Map (CMap) to prioritize adverse events hypotheses. Finally, we accepted higher-confidence hypotheses that have been predicted by independent approaches. Our results reveal that the mRNA-based BNT162b2 vaccine affects immune response pathways related to interferon and cytokine signaling, which should lead to vaccine success, but may also result in some adverse events. Our results emphasize the effects of BNT162b2 on calcium homeostasis, which could be contributing to some frequently encountered adverse events related to mRNA vaccines. Notably, cardiac side effects were signaled in the CMap query results. In summary, our approach has identified mechanisms underlying both the expected protective effects of vaccination as well as possible post-vaccine adverse effects. Our study illustrates the power of systems biology approaches in improving our understanding of the comprehensive biological response to vaccination against COVID-19.https://www.mdpi.com/2076-0817/11/7/743COVID-19mRNA vaccineinformatics workflowSARS-CoV-2systems biologyvaccine adverse events |
| spellingShingle | Rima Hajjo Dima A. Sabbah Alexander Tropsha Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects Pathogens COVID-19 mRNA vaccine informatics workflow SARS-CoV-2 systems biology vaccine adverse events |
| title | Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects |
| title_full | Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects |
| title_fullStr | Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects |
| title_full_unstemmed | Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects |
| title_short | Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects |
| title_sort | analyzing the systems biology effects of covid 19 mrna vaccines to assess their safety and putative side effects |
| topic | COVID-19 mRNA vaccine informatics workflow SARS-CoV-2 systems biology vaccine adverse events |
| url | https://www.mdpi.com/2076-0817/11/7/743 |
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