Study exploring the immune response generated by PHH-1V81 XBB.1.16 or BNT162b2 XBB.1.15, particularly focusing on the antibodies produces by B cells following a booster dose of vaccines adapted to XBB variants. Both vaccines significantly increase the activation of memory B cells with cross-reactivity against both the ancestral and the vaccine variant. Notably, the cross-reactive B cells targeting Wuhan-Hu-1 and XBB.1.16 in the PHH-1V81 XBB.1.16 arm were associated with a stronger neutralizing response, reinforcing the potential of PHH-1V81 as a powerful booster candidate against emerging variants.