Tracking B Cell Responses to the SARS-CoV-2 mRNA-1273 Vaccine

ABSTRACT: The COVID-19 pandemic left an unprecedented social and economic impact on the world. This rapidly evolving global instigated a worldwide effort to develop an effective vaccine. Despite the generation of a protective antibody response in most individuals after two doses of an anti-spike mRNA vaccine, some studies have shown that a poorer response is elicited in some individuals, particularly those that are immunocompromised or elderly. To gain further insight into the cellular mechanisms driving B cell evolution in response to vaccination against SARS-CoV-2, we performed longitudinal single-cell transcriptomic, epitope sequencing (CITE-seq), and repertoire profiling of three COVID-19 vaccinees. Spike-specific (S-2P+) B cells showed early immune activation at v1D14 (14 days after vaccine dose 1) and accumulation of somatic hyper mutation (SHM) up to v2M6 (months 6). At v2D6, the S-2P+ cells expanded into memory B cell (MBC) cluster 5 with a dynamic kinetics over time. At v2M6, majority of S-2P+ cells were into resting memory (RM) subset within cluster 5. Analysis of B cell receptor (BCR) repertoire showed selection of genes commonly detected in neutralizing monoclonal antibodies from COVID-19 patients. Tracking of S-2P+ B cell response showed clonal association between earlier activated CD38+ memory, as well as tissue-like memory, with RM B cells at v2M6. These clones showed evolving signal with progressive accumulation of SHM over time. The presence of early plasmablast (PB) within these clones corroborates our previous report that associates PB response with sustained immunity. This integrated analysis allowed us to characterize the transcriptional activity underpinning the development of B cells involved in inducing an immune response to the COVID-19 vaccine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE219098 | GEO | 2023/07/07

REPOSITORIES: GEO