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High-dimensional assessment of B cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

ABSTRACT: Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination, and 7, 21, and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92884 | GEO | 2016/12/26

SECONDARY ACCESSION(S): PRJNA358723

REPOSITORIES: GEO

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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)

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High-dimensional assessment of B cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

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