This study investigated the impact of previous SARS-CoV-2 infection and vaccination on immune responses to a third BNT162b2 vaccine dose and the risk of Omicron breakthrough infection. The study found that prior infection significantly enhanced humoral and cellular responses post-vaccination, particularly IgA responses. Lower post-vaccination IgG, IgA, and neutralizing antibody levels were strongly associated with a higher risk of reinfection and future Omicron infections, while T-cell responses showed no such association. Prior infection before Omicron, followed by Omicron reinfection, dampened subsequent humoral and cellular responses, consistent with immune imprinting. Robust humoral responses, particularly IgA, were crucial in preventing future infections.

Laura Pérez-Alós, Cecilie Bo Hansen, Jose Juan Almagro Armenteros, Johannes Roth Madsen, Line Dam Heftdal, Rasmus Bo Hasselbalch, Mia Marie Pries-Heje, Rafael Bayarri-Olmos, Ida Jarlhelt, Sebastian Rask Hamm, Dina Leth Møller, Erik Sørensen, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Linda Maria Hilsted, Henning Bundgaard, Susanne Dam Nielsen, Kasper Karmark Iversen, Peter Garred