Progressive Dissociation Between Reactogenicity and Immunogenicity After Four-Dose BNT162b2 Vaccination: A 36-Month...

Area of Science:

• Immunology
• Vaccinology
• Public Health

Background:

• Understanding the relationship between vaccine side effects (reactogenicity) and immune response (immunogenicity) is key for optimizing vaccination schedules.
• Repeated dosing of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine has shown varying levels of reactogenicity and immunogenicity.

Purpose of the Study:

• To quantify the progressive dissociation between reactogenicity and immunogenicity across four doses of the BNT162b2 vaccine.
• To analyze the correlation between local/systemic reactions and antibody titers after repeated vaccination.

Main Methods:

• A prospective longitudinal cohort study involving 631 Croatian healthcare workers vaccinated with BNT162b2.
• Measurement of anti-SARS-CoV-2 IgG antibodies at 16 timepoints using chemiluminescent immunoassay.
• Recording of local and systemic reactions using the FDA toxicity scale and correlation analysis with Spearman's method.

Main Results:

• Local reactions decreased from 82.4% after the first dose to 42.9% after the fourth (p < 0.001).
• Systemic reactions peaked after the second dose and decreased with subsequent doses, while median antibody levels increased significantly after the third and fourth doses.
• The correlation between vaccine reactions and antibody titers progressively weakened with each successive dose.

Conclusions:

• A dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 vaccine doses.
• Booster doses of the BNT162b2 vaccine maintain robust antibody responses despite reduced local and systemic reactions.
• Minimal side effects following COVID-19 vaccine boosters are consistent with sustained humoral immunity.