Longitudinal proteomic and autoantibody signatures after mRNA vaccination in healthy individuals
Bibliographic record
Abstract
Longitudinal analysis of the circulating proteome after SARS-CoV-2 mRNA vaccination provides insights into immune adaptation, optimizing vaccination strategies, and understanding long-term molecular effects. We analyzed 120 paired plasma samples from 114 healthy participants at six time points: pre-vaccination, 3 days and 7–21 days post-dose 1, 7–21 days post-dose 2, and at 8-, 16-, and 24-weeks post-dose 2. IgG antibody responses to SARS-CoV-2 structural proteins and autoantibody profiles were assessed using a multiplex platform, and plasma proteome changes were quantified by mass spectrometry. IgG antibodies against spike protein regions (RBD, S1, S2) produced sustained responses for up to 24 weeks, with no detection of nucleocapsid or membrane antibodies, confirming that there was no prior infection. Younger participants (<45 years) presented stronger responses, with no significant sex differences. Proteomics identified 342 proteins, of which 214 proteins were significantly altered, predominantly at 16–24 weeks. Key changes included upregulation of C1 complex proteins (C1R, C1QC, C1S) and downregulations of the C1 inhibitor SERPING1, indicating complement activation. Platelet-associated proteins showed minimal changes, suggesting a limited thrombosis risk. Altered proteins were enriched in carbohydrate metabolism, cofactors/vitamin metabolism, and thyroid hormone pathways. Autoantibody profiling showed stable responses for most self-antigens, with modest increased in several interleukin specific autoantibodies, including IL-1B, at later time points. Integrated plasma proteomics and autoantibody profiling demonstrated sustained immunogenicity and safety of SARS-CoV-2 mRNA vaccines, characterized by durable spike-specific antibody responses, late-onset complement activation, and limited autoantibody induction. These findings enhance our understanding of vaccine-induced immunity and inform long-term monitoring and optimization of mRNA vaccine strategies. • IgG antibodies against spike protein regions (RBD, S1, and S2) remained robust and stable for up to 24 weeks after SARS-CoV-2 mRNA vaccination. • Plasma proteomics showed major protein changes at 16–24 weeks, consistent with immune and complement activation. • Increased C1R,C1QC,C1S and decreased SERPING1 suggest vaccine-induced activation of the classical complement pathway. • Autoantibody profiling revealed stable self-antigen responses, with increased reactivity against IL-1B but no induction of type I or type III interferon autoantibodies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".