PT  - JOURNAL ARTICLE
AU  - Richert, Laura
AU  - Lelièvre, Jean-Daniel
AU  - Lacabaratz, Christine
AU  - Hardel, Lucile
AU  - Hocini, Hakim
AU  - Wiedemann, Aurélie
AU  - Lucht, Frédéric
AU  - Poizot-Martin, Isabelle
AU  - Bauduin, Claire
AU  - Diallo, Alpha
AU  - Rieux, Véronique
AU  - Rouch, Elodie
AU  - Surenaud, Mathieu
AU  - Lefebvre, Cécile
AU  - Foucat, Emile
AU  - Tisserand, Pascaline
AU  - Guillaumat, Lydia
AU  - Durand, Mélany
AU  - Hejblum, Boris
AU  - Launay, Odile
AU  - Thiébaut, Rodolphe
AU  - Lévy, Yves
TI  - 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
AID  - 10.4049/jimmunol.2101076
DP  - 2022 May 25
TA  - The Journal of Immunology
PG  - ji2101076
4099  - http://www.jimmunol.org/content/early/2022/05/24/jimmunol.2101076.short
4100  - http://www.jimmunol.org/content/early/2022/05/24/jimmunol.2101076.full
AB  - We evaluated four heterologous prime-boost HIV vaccine strategies in a clinical trial.Three strategies, all including the HIV MVA-B vaccine, led to T cell responses.A gene expression signature related to the HIV MVA-B vaccine was identified.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.