Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. 12/19/2022. Cao Y. Nature.

Immune imprinting occurs when exposure to an original viral strain prevents our bodies from producing sufficient neutralizing antibodies (NAb) against diverse new strains of that virus.

Unprecedented numbers of Omicron BA.5 variants are emerging (including BQ.1.1.10, and XBB) that for unclear reasons display mutations that converge at same antibody-evasive hotspots on the receptor-binding domain (RBD). These investigators demonstrate that vaccination with BA.2 and BA.5 mainly recalls the same cross-reactive memory B cells elicited previously by wildtype-based vaccine, but rarely produce novel BA.2/BA.5 specific B cells, and therefore, no new divergent antibodies specific for the mutant hotspots. However, the NAbs still maintain sufficient ACE2 binding capability and will fight the novel-mutant infections. Immune imprinting also reduced the diversity of the NAb binding sites and increased proportions of non-neutralizing antibody clones. Reduced diversity focused humoral immune pressure and promoted convergent mutational evolution in the untargeted RBD hotspots.

SAB Comment: These results suggest that our current herd immunity whether produced by natural infection and/or by inactivated vaccines or mRNA vaccines, may impede our ability to fight emerging Omicron variants. Immune imprinting (a.k.a., “original sin”) will inhibit our capacity to synthesize novel antibodies to recognize these new convergent mutations in Omicron variants. Recent clinical trials bear out this prediction. The bivalent boosters may be no better than the monovalents in eliciting novel variant-fighting antibodies.

https://www.nature.com/articles/s41586-022-05644-7