# Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera

## TL;DR

This study explores how mRNA vaccines affect immune responses in men and women, using proteomics to identify markers linked to antibody levels after vaccination.

## Contribution

The study introduces a proteomic approach to identify predictors of long-term antibody responses to SARS-CoV-2 vaccines.

## Key findings

- Female mRNA-1273 recipients showed upregulated inflammatory and immunological responses one month post-third vaccination.
- A Random Forest model identified 85 proteomic markers predictive of robust IgG responses six months after vaccination.
- Thirty key markers were linked to complement cascade, IL-17, and cell cycle progression pathways.

## Abstract

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.

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.

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.

These results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.