ART4 and infection: Moreover, the majority of the vaccines were developed based on the S glycoprotein, RBD domain, or inactivated virus of the ancestral Wuhan-Hu-1 strain, and recent work has shown that this immunological background can be counterproductive due to immune imprinting or antigen sin, so the antibodies elicited after breakthrough infection remain primarily activated against ancestral strains, leading to poor efficacy against new emerging variants8,20,21.