Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions

Area of Science:

• Immunology
• Vaccinology
• Allergy and Immunology

Background:

• Immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines, particularly the Pfizer-BioNTech (BNT162b2) vaccine, lack clear underlying immunological mechanisms.
• Understanding these reactions is crucial for vaccine safety and public trust.

Purpose of the Study:

• To investigate the immunological mechanisms of immediate-type HSR to the BNT162b2 vaccine.
• To examine antibody responses, specifically to polyethylene glycol (PEG), after vaccination.

Main Methods:

• Blood samples were collected from BNT162b2 vaccine reactors (n=47) and non-reactors (n=67).
• Measured were Immunoglobulin (Ig)G, IgM, and IgE antibodies to the vaccine, biomarkers like tryptase, complement 5a (C5a), intercellular adhesion molecule 1 (ICAM-1), and cytokines (IL-4, IL-10, IL-33, TNF, MCP-1).
• Basophil activation tests (BAT) were performed on anaphylaxis patients.

Main Results:

• Most BNT162b2 vaccine HSR patients had elevated C5a and Th2 cytokines but normal tryptase levels.
• Vaccine reactors exhibited significantly higher IgM antibodies to the BNT162b2 vaccine compared to non-reactors (median 67.2 vs. 23.9 AU/mL, p < 0.001).
• No IgE antibodies to the vaccine were detected, and BAT results for the vaccine and its components were negative in anaphylaxis patients.

Conclusions:

• Acute hypersensitivity reactions to the BNT162b2 vaccine appear to be pseudo-allergic, driven by C5a activation and independent of IgE.
• Elevated anti-BNT162b2 IgM levels in reactors suggest a role, though its exact function requires further investigation.