T Cell Immunogenicity, Gene Expression Profile, and Safety of Four Heterologous Prime-Boost Combinations of HIV Vaccine Candidates in Healthy Volunteers: Results of the Randomized Multi-Arm Phase I/II ANRS VRI01 Trial
RICHERT, Laura
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
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Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
RICHERT, Laura
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
HARDEL, Lucile
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
BAUDUIN, Claire
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
ROUCH, Elodie
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
DURAND, Melany
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
HEJBLUM, Boris
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
THIEBAUT, Rodolphe
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
< Réduire
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Langue
EN
Article de revue
Ce document a été publié dans
Journal of Immunology. 2022-06-15, vol. 208, n° 12, p. 2663-2674
Résumé en anglais
Heterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T cell responses. In this phase I/II multi-arm trial, three vaccine ...Lire la suite >
Heterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T cell responses. In this phase I/II multi-arm trial, three vaccine candidates were used as prime or boost: modified vaccinia Ankara (MVA) HIV-B (coding for Gag, Pol, Nef); HIV LIPO-5 (five lipopeptides from Gag, Pol, Nef); DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, Env gp160 clade B). Healthy human volunteers (n = 92) were randomized to four groups: 1) MVA at weeks 0/8 + LIPO-5 at weeks 20/28 (M/L); 2) LIPO-5 at weeks 0/8 + MVA at weeks 20/28 (L/M); 3) DNA at weeks 0/4/12 + LIPO-5 at weeks 20/28 (G/L); 4) DNA at weeks 0/4/12 + MVA at weeks 20/28 (G/M). The frequency of IFN-γ–ELISPOT responders at week 30 was 33, 43, 0, and 74%, respectively. Only MVA-receiving groups were further analyzed (n = 62). Frequency of HIV-specific cytokine-positive (IFN-γ, IL-2, or TNF-α) CD4+ T cells increased significantly from week 0 to week 30 (median change of 0.06, 0.11, and 0.10% for M/L, L/M, and G/M, respectively), mainly after MVA vaccinations, and was sustained until week 52. HIV-specific CD8+ T cell responses increased significantly at week 30 in M/L and G/M (median change of 0.02 and 0.05%). Significant whole-blood gene expression changes were observed 2 wk after the first MVA injection, regardless of its use as prime or boost. An MVA gene signature was identified, including 86 genes mainly related to cell cycle pathways. Three prime-boost strategies led to CD4+ and CD8+ T cell responses and to a whole-blood gene expression signature primarily due to their MVA HIV-B component.< Réduire
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