Dataset Information

Pre-existing memory B cell phenotypes determine the quality of B cell response to vaccine boosters

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282932 | GEO | 2026/01/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Successful development of HIV-vaccination strategies will also depend on the ability to use novel approaches to analyse and integrate immunogenicity data generated in vaccine trials. The ANRS VAC 18 trial evaluated the immunogenicity of HIV-LIPO-5 vaccine (5 HIV peptides coupled to a palmytoil tail) administered at W0, 4, 12 and 24 in healthy volunteers. 62-69% of vaccinees developed HIV-specific ELISpot responses by W26. Here we present extensive immunogenicity assessments in a subset of vaccinees using ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses. Peripheral blood mononuclear cells from volunteers collected before and following vaccinations were stimulated with HIV LIPO 5 vaccine, Gag peptides contained or not in the vaccine as controls. Different time points and stimulation conditions were compared, using false discovery rate to control for test multiplicity. 74% and 30% of vaccinees had cultured ELISpot and lymphoproliferation responses at W14, respectively. Ex-vivo ICS showed mainly single IL-2 producing cells. Secretion of IFN-Î³, TNF-Î±, IL-5, and IL-13 increased significantly in response to Gag stimulation after culture at W14 compared to W0. An induction of metallothionein genes was consistently detected after HIV-LIPO-5 stimulation at W0 and W14 related to the adjuvant effect of the lipid tail. After vaccination (W14), significant probes increased substantially (>1200 probes) including IFN-Î³, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6 W14 (fold change > 100%). In conclusion, HIV LIPO-5 vaccination elicited memory precursor responses with a Th1 and Th2 profile. The signature profile before vaccination provides information about the adjuvant effect of the lipid tail. Consistently with cytokine responses, vaccination is associated with a modulation in gene expression. This combined approach allowed to identify new signatures of HIV vaccine response and indicates that HIV-LIPO-5 could be further developed as a prime component of heterologous prime boost strategies. PBMC mRNA of 12 healthy volunteers, stimulate in four different conditions (HIV-LIPO-5, Gag+, Gag-, NS) during 6 and 24 hours before and after vaccination (week 0 and week 14)

Dataset Information

Pre-existing memory B cell phenotypes determine the quality of B cell response to vaccine boosters

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets