Comparative immunologic profiling of mRNA and protein-conjugated vaccines: acute inflammatory responses and anti-PEG antibody production

Messenger ribonucleic acid (mRNA) vaccines have become a prevalent immunization method, even as the coronavirus disease 2019 (COVID-19) pandemic recedes. However, the potential adverse effects using mRNA vaccines need to be explored in this evolving landscape. In this study, 60 participants were randomly assigned to receive either an mRNA vaccine, specifically for COVID-19, or a conventional vaccine for meningococcal disease. Symptom records and blood samples were collected on Days 0, 3, and 7 after vaccination. Results showed that recipients of mRNA vaccines exhibited elevated levels of serum acute-phase proteins, such as haptoglobin and C-reactive protein, alongside decreased white blood cell counts compared to those receiving conventional vaccines. Proteomic analysis identified significant changes in nine proteins, including interactions involving complement component C9, haptoglobin, and alpha-1-acid glycoprotein, suggesting implications for complement activation and inflammatory responses. Furthermore, variability in anti-polyethylene glycol antibody levels was noted among mRNA vaccine recipients compared to conventional vaccine recipients. This research aims to provide useful information to help develop future vaccination strategies and shape research directions to mitigate individual adverse effects.