Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera
IntroductionThe first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502458/full |
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| author | Thomas E. Hickey Uma Mudunuri Heidi A. Hempel Troy J. Kemp Nancy V. Roche Keyur Talsania Brian A. Sellers James M. Cherry Ligia A. Pinto |
| author_facet | Thomas E. Hickey Uma Mudunuri Heidi A. Hempel Troy J. Kemp Nancy V. Roche Keyur Talsania Brian A. Sellers James M. Cherry Ligia A. Pinto |
| author_sort | Thomas E. Hickey |
| collection | DOAJ |
| description | IntroductionThe first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.MethodsAn aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.ResultsSera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.DiscussionThese results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination. |
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| id | doaj-art-8b9230ee79954559a32ece1c11a355dc |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-8b9230ee79954559a32ece1c11a355dc2025-01-27T06:40:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15024581502458Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient seraThomas E. Hickey0Uma Mudunuri1Heidi A. Hempel2Troy J. Kemp3Nancy V. Roche4Keyur Talsania5Brian A. Sellers6James M. Cherry7Ligia A. Pinto8Vaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesAdvanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesAdvanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesCenter for Human Immunology, Inflammation and Autoimmunity, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesCenter for Human Immunology, Inflammation and Autoimmunity, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesVaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, United StatesIntroductionThe first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.MethodsAn aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.ResultsSera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.DiscussionThese results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502458/fullserologyproteomicsSARS-CoV-2mRNA-1273BNT162b2vaccine response |
| spellingShingle | Thomas E. Hickey Uma Mudunuri Heidi A. Hempel Troy J. Kemp Nancy V. Roche Keyur Talsania Brian A. Sellers James M. Cherry Ligia A. Pinto Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera Frontiers in Immunology serology proteomics SARS-CoV-2 mRNA-1273 BNT162b2 vaccine response |
| title | Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera |
| title_full | Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera |
| title_fullStr | Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera |
| title_full_unstemmed | Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera |
| title_short | Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera |
| title_sort | proteomic and serologic assessments of responses to mrna 1273 and bnt162b2 vaccines in human recipient sera |
| topic | serology proteomics SARS-CoV-2 mRNA-1273 BNT162b2 vaccine response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1502458/full |
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