J Virol

In this placebo-controlled phase II randomized clinical trial, 103 HIV-1 infected patients under c-ART (combined antiretroviral treatment) were randomized 2:1 to receive 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag and gp160) at Week (W)0, W4 and W12 followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol and Nef at W20 and W24 or placebos. Analytical treatment interruption (ATI) was performed between W36 to W48.At W28, vaccinees experienced an increase in functional CD4(+) T cell responses measured (P\textbackslashtextless0.001 for each cytokine compared to W0) predominantly against Gag and Pol/Env and an increase in HIV-specific CD8(+) T cells producing IL-2 and TNF-α (P=0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T cell subsets by mass cytometry in a subpopulation showed an increase of W28/W0 ratio for memory CD8(+) T cells co-expressing exhaustion and senescence markers such as PD-1/TIGIT (P=0.004) and CD27/CD57 (P=0.044) in vaccinees compared to placebo. During ATI, all patients experienced viral rebound with a maximum observed HIV RNA level at W42 (median: 4.63 log(10) cp/ml; IQR 4.00-5.09) without any difference between arms. No patient resumed c-ART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed.These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need of combined immunomodulatory strategies.IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU®-MultiHIV B clade) followed by a boost vaccination by a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients while on combined antiretroviral therapy. We show that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1 infected individuals and healthy volunteers who received each vaccine component individually. Compared to placebo group, vaccines elicited strong and polyfunctional HIV-specific CD4(+) and CD8(+) T cell responses. However, these immune responses presenting some qualitative defects were not able to control viremia following antiretroviral treatment interruption as no difference in HIV viral rebound was observed in vaccine and placebo groups. Several lessons were learned from these results pointing out the urgent need to combine the vaccine strategies with other immune-based interventions

GLOBAL HYBRID STRATEGY FOR MULTI-SCALE CHARACTERIZATION OF COMPOSITE MATERIAL PROPERTIES WITH NON-DESTRUCTIVE TESTS

International audienceOne of the main issues of composite materials is related to the difficulty of characterizing the full set of material properties at both mesoscopic and microscopic scales. Indeed, classical mechanical tests (traction/compression, 3 and 4 points bending tests, etc.) are not able to provide the full set of 3D material properties of composites. Furthermore, these tests can usually provide only the in-plane elastic properties of the constitutive lamina (i.e. at. the mesoscopic scale). Therefore, to go beyond the main restrictions imposed by standard destructive tests, this work deals with the desire of characterizing the material properties of a composite plate, at each characteristic scale, through a single non-destructive dynamic test performed at the macroscopic scale, i.e. that of the specimen. To face such a problem a general multi-scale identification strategy (MSIS) is proposed. The MSIS aims at identifying the constitutive properties at both micro and meso-scales by exploiting the information restrained in the laminate macroscopic dynamical response. In this context it is possible to characterize both elastic and viscoelastic micro-scale properties. The MSIS relies on the one hand on the strain energy homogenization technique of periodic media (to get the effective material properties of the lamina as a function of the geometrical and material properties of the microscopic constitutive phases) and on the other hand on a specific hybrid algorithm (genetic + gradient-based algorithm) to perform the solution search for the problem. The identification problem is stated as a constrained inverse problem (a least-square constrained problem), where the objective function depends upon both the measured (from experiments) and numerical (from FE analysis) dynamic response of the plate. In order to validate the effectiveness of the MSIS, the measured dynamic response is obtained, in a first time, by using a numerical test conducted on a reference structure, to check the robustness and the reliability of the proposed methodology. The optimization variables are both geometrical and material properties of the constitutive phases composing the representative volume element of the composite. In the end, the effectiveness of the MSIS is then validated through a campaign of experimental/numerical tests conducted on composite laminates