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Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization

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**Reminder:** This post contains a **preprint** that has **not been peer-reviewed.** Readers should be aware that preprints have not been finalized by authors, may contain errors, and report info that has **not yet been accepted or endorsed in any way by the scientific or medical community.** *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/COVID19) if you have any questions or concerns.*


BillyGrier

Last paragraph of conclusion: ____ Our observation that mice boosted homologously with WH1 mRNA had only slightly (and not significantly) lower whole-IgG titers against RBDs of both strains than mice boosted with BA.1 mRNA is in agreement with data from non-human primates in showing that neutralizing antibodies to both strains are similarly induced by homologous and heterologous boosting. The same study found similar expansion of cross-reactive memory B cells in both groups, as also reported for Omicron breakthrough infections in WH1-vaccinated humans[37, 38]. However, deconvolution of antibody responses into primary and boost-elicited clones using the K-tag system revealed that heterologous boosting was uniquely capable of recruiting new, BA.1-specific B cell clones with greater neutralizing potency towards the variant strain. Importantly, a second dose of BA.1 was required to amplify this new antibody reactivity, most likely because it directed memory B cells generated by the first BA.1 boost into the plasma cell compartment. Barring major differences in the logic of imprinting/OAS between humans and mice, **our findings suggest that Omicron-specific boosters will induce B cell clones that are superior neutralizers of Omicron strains, although their full effectiveness may be best measured after a second heterologous booster dose.** Our findings therefore contribute to the ongoing debate on the value of Omicron-specific boosters for the broadening of protection to SARS-CoV-2.