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

• Published in: The Journal of immunology (1950) Vol. 208; no. 12; pp. 2663 - 2674
• Main Authors: Richert, Laura, Lelièvre, Jean-Daniel, Lacabaratz, Christine, Hardel, Lucile, Hocini, Hakim, Wiedemann, Aurélie, Lucht, Frédéric, Poizot-Martin, Isabelle, Bauduin, Claire, Diallo, Alpha, Rieux, Véronique, Rouch, Elodie, Surenaud, Mathieu, Lefebvre, Cécile, Foucat, Emile, Tisserand, Pascaline, Guillaumat, Lydia, Durand, Mélany, Hejblum, Boris, Launay, Odile, Thiébaut, Rodolphe, Lévy, Yves
• Format: Journal Article
• Language: English
• Published: United States Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists 15-06-2022
• Subjects: Immunology; Life Sciences; Microbiology and Parasitology; Quantitative Methods; Vaccinology; Virology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2101076

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 (
= 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 (
= 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.