Fig. 1: Molecular fate-mapping to decipher OAS.
From: Fate-mapping antibodies to study sinful immune dynamics
a, Schiepers et al.2 designed a mouse model wherein the administration of tamoxifen after primary immunization or infection labels all antibodies derived from the primary germinal center B cells with a Strep tag. Upon cessation of tamoxifen treatment, any antibodies produced by subsequent secondary or tertiary immunization will be tagged with Flag. b,c, Using this model, the authors showed that sequential immunization with SARS-CoV-2 spike mRNA vaccines (b) and influenza hemagglutinins (c) elicits an ‘addiction’ to clones from the primary cohort, and a suppression of de novo secondary clonal activation. Although this effect was strong in the case of homologous antigen exposure (b,c, top row), immunization with drifted variants both updated the antibody repertoire and largely, but not completely, mitigated de novo suppression (b,c, bottom row(s)). These findings suggest that booster vaccines for viral variants serve a crucial function in diversifying the antibody repertoire, but that new secondary antibody clones are in fact inhibited in an OAS-like manner, to a degree dependent on antigenic distance. Figure created using BioRender (biorender.com).
