Pre-existing memory B cell phenotypes determine the quality of B cell response to vaccine boosters
Different COVID-19 vaccine modalities expressing the same SARS-CoV-2 spike antigen present a unique opportunity to contrast the immunologic outcomes associated with each vaccine platform. Here we characterized the memory B cell response elicited by 12 different combinations of primary series and boost vaccines spanning adenovirus vector, mRNA and subunit protein technologies. Cross-reactive B cells for ancestral virus and Omicron BA.1 expanded in similar proportions across all vaccine regimens. However, mRNA boost following adenovirus vector prime resulted in the greatest increase in antigen-specific B cell frequencies, predominantly of a highly activated 'atypical' B cell subset, identified by flow cytometry and single-cell sequencing. Using lineage tracking by single-cell IG sequencing we characterized B cell lineages exhibiting different phenotypes at subsequent time-points. Furthermore, the same mRNA boost induced markedly different memory B cell phenotypes depending on the modality of the prime, suggesting that the type of response elicited by boosting is dependent on the nature of pre-existing memory B cells imprinted by the vaccine priming. Overall design: SARS-CoV-2-specific B cells were sorted from PBMC samples from people vaccinated with either Janssen Ad26.COV2.S, Moderna mRNA-1273, or Pfizer/BioNTech BNT162b2 and boosted with either these vaccines or Novavax NVX-CoV2373 at pre-boost, 2 weeks post-boost and 6 months post-boost.These cells were processed using the 10x Chromium for single cell sequencing.