tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jan 27:15:1502458.
doi: 10.3389/fimmu.2024.1502458. eCollection 2024. Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera
Thomas E Hickey[SUP] #[/SUP][SUP] 1 [/SUP], Uma Mudunuri[SUP] #[/SUP][SUP] 2 [/SUP], Heidi A Hempel[SUP] 1 [/SUP], Troy J Kemp[SUP] 1 [/SUP], Nancy V Roche[SUP] 1 [/SUP], Keyur Talsania[SUP] 2 [/SUP], Brian A Sellers[SUP] 3 [/SUP], James M Cherry[SUP] 3 [/SUP], Ligia A Pinto[SUP] 1 [/SUP]
Affiliations
Introduction: The 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.
Methods: An 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.
Results: Sera 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.
Discussion: These results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.
Keywords: BNT162b2; SARS-CoV-2; mRNA-1273; proteomics; serology; vaccine response.
. 2025 Jan 27:15:1502458.
doi: 10.3389/fimmu.2024.1502458. eCollection 2024. Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera
Thomas E Hickey[SUP] #[/SUP][SUP] 1 [/SUP], Uma Mudunuri[SUP] #[/SUP][SUP] 2 [/SUP], Heidi A Hempel[SUP] 1 [/SUP], Troy J Kemp[SUP] 1 [/SUP], Nancy V Roche[SUP] 1 [/SUP], Keyur Talsania[SUP] 2 [/SUP], Brian A Sellers[SUP] 3 [/SUP], James M Cherry[SUP] 3 [/SUP], Ligia A Pinto[SUP] 1 [/SUP]
Affiliations
- PMID: 39931577
- PMCID: PMC11808009
- DOI: 10.3389/fimmu.2024.1502458
Introduction: The 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.
Methods: An 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.
Results: Sera 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.
Discussion: These results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.
Keywords: BNT162b2; SARS-CoV-2; mRNA-1273; proteomics; serology; vaccine response.