Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Current COVID-19 vaccines, including mRNA and viral vector types, primarily use the spike glycoprotein as the immunogen.
• mRNA vaccines are known to reactivate pre-existing cross-reactive immunity, but the effect of viral vector vaccines remains unclear.

Purpose of the Study:

• To investigate and compare cellular and humoral immune responses following heterologous (AZ-BNT) and homologous (BNT-BNT) COVID-19 vaccination regimens.
• To determine if adenovirus-vector-based vaccination reactivates pre-existing cross-reactive immunity.

Main Methods:

• Studied cellular and humoral immune responses in individuals receiving heterologous ChAdOx1 nCOV-19 (AZ) and BNT162b2 (BNT) vaccination.
• Compared these responses to those in individuals receiving homologous BNT-BNT vaccination.
• Analyzed antibody titers, epitope coverage, and T cell receptor (TCR) repertoire breadth.

Main Results:

• Primary AZ vaccination did not significantly reactivate cross-reactive cellular and humoral immunity compared to primary BNT vaccination.
• AZ vaccination induced distinct humoral responses, including differences in spike peptide epitope coverage and a lack of anti-S2 IgG antibodies.
• Secondary BNT vaccination in heterologous recipients reactivated pre-existing immunity, similar to homologous mRNA vaccination.

Conclusions:

• Primary vaccination with adenovirus-vector (AZ) and mRNA (BNT) vaccines elicits different immune response patterns despite targeting the same antigen.
• Heterologous vaccination strategies, particularly with a BNT booster, can restore reactivated cross-reactive immunity.
• Further research is needed to understand the implications of these differing immune responses for vaccine and schedule development.