Human Gene Set: RICHERT_PBMC_HIV_LIPO_5_AGE_37_48YO
      _STIMULATED_VS_UNSTIMULATED_14W
      _SIGNIFICANT_VARIATION_UP


Standard name RICHERT_PBMC_HIV_LIPO_5_AGE_37_48YO_STIMULATED_VS_UNSTIMULATED_14W_SIGNIFICANT_VARIATION_UP
Systematic name M41027
Brief description Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in adults (37-48) after exposure to HIV-LIPO-5 , time point 14W. Comment: genes with a significant variation at W14 after 24-h HIV-LIPO-5 stimulation, IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6 were overexpressed with a fold change |FC| >1.8
Full description or abstract OBJECTIVE: To dissect the biological mechanisms involved in the cellular responses to a candidate vaccine containing 5 HIV peptides coupled to a palmytoil tail (HIV-LIPO-5) in healthy volunteers, by using extensive immunogenicity assessments with different stimulation durations. DESIGN: Immunogenicity substudy of a randomized phase II prophylactic HIV vaccine trial (ANRS VAC 18). METHODS: HIV-LIPO-5 or placebo was administered at W0, W4, W12 and W24. Peripheral blood mononuclear cells from a subset of participants at W0 and W14 were stimulated with HIV-LIPO-5, Gag peptides contained in the vaccine and control peptides. ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses were performed. Different time points and stimulation conditions were compared, controlling for test multiplicity. RESULTS: Cultured ELISpot and lymphoproliferation responses were detected at W14. Ex-vivo ICS showed mainly interleukin (IL)-2-producing cells. Secretion of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-5 and IL-13 increased significantly after culture and Gag stimulation at W14 compared to W0. Metallothionein genes were consistently overexpressed after HIV-LIPO-5 stimulation at W0 and W14. At W14, significant probes increased substantially, including IFN-gamma, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6. Canonical pathway analyses indicated a role of interferon signalling genes in response to HIV-LIPO-5. CONCLUSION: HIV-LIPO-5 vaccination elicited Th1 and Th2 memory precursor responses and a consistent modulation in gene expression. The response profile before vaccination suggests an adjuvant effect of the lipid tail of HIV-LIPO-5. Our combined immunogenicity analyses allowed to identify a specific signature profile of HIV-LIPO-5 and indicate that HIV-LIPO-5 could be further developed as a prime in heterologous prime-boost strategies.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 23759749   Authors: Richert L,Hue S,Hocini H,Raimbault M,Lacabaratz C,Surenaud M,Wiedemann A,Tisserand P,Durier C,Salmon D,Lelièvre JD,Chêne G,Thiébaut R,Lévy Y,ANRS Vaccine Network/Vaccine Research Institute
Exact source Results: Modulation of gene expression by HIV-LIPO-5
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External links https://www.ncbi.nlm.nih.gov/pubmed/?term=23759749
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Source species Homo sapiens
Contributed by HIPC SIGNATURES (NIAID/HIPC SIGNATURES)
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