VaccineNov 28, 2025

Changes in protein and immune antibody patterns over time after mRNA vaccination in healthy people

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

IgG antibodies against spike protein regions showed sustained responses for up to 24 weeks after SARS-CoV-2 mRNA vaccination.

Younger participants (<45 years) exhibited stronger antibody responses, with no significant differences observed between sexes.
Proteomics analysis identified 342 proteins, with 214 showing significant alterations, particularly at 16-24 weeks post-vaccination.
Key changes included upregulation of complement proteins and downregulation of the C1 inhibitor, suggesting complement activation.
Platelet-associated proteins exhibited minimal changes, indicating a limited risk of thrombosis.
Altered proteins were primarily associated with carbohydrate metabolism, cofactors/vitamin metabolism, and thyroid hormone pathways.
Autoantibody profiling revealed stable responses for most self-antigens, with modest increases in certain interleukin-specific autoantibodies at later time points.

Simplified

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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Changes in protein and immune antibody patterns over time after mRNA vaccination in healthy people

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