Trials

INTRODUCTION: The Ebola virus disease (EVD) outbreak in 2014-2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. METHODS: This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. RESULTS: From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12-17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. DISCUSSION: The PREVAC trial is evaluating-placebo-controlled-two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. TRIAL REGISTRATION: ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016

Targeting respiratory complex I to prevent the Warburg effect.

In the last 10 years, studies of energetic metabolism in different tumors clearly indicate that the definition of Warburg effect, i.e. the glycolytic shift cells undergo upon transformation, ought to be revisited considering the metabolic plasticity of cancer cells. In fact, recent findings show that the shift from glycolysis to re-established oxidative metabolism is required for certain steps of tumor progression, suggesting that mitochondrial function and, in particular, respiratory complex I are crucial for metabolic and hypoxic adaptation. Based on these evidences, complex I can be considered a lethality target for potential anticancer strategies. In conclusion, in this mini review we summarize and discuss why it is not paradoxical to develop pharmacological and genome editing approaches to target complex I as novel adjuvant therapies for cancer treatment

The MUGAST-AGATA-VAMOS campaign: Set-up and performances

none50The MUGAST-AGATA-VAMOS set-up at GANIL combines the MUGAST highly-segmented silicon array with the state-of-the-art AGATA array and the large acceptance VAMOS spectrometer. The mechanical and electronics integration copes with the constraints of maximum efficiency for each device, in particular γ-ray transparency for the silicon array. This complete set-up offers a unique opportunity to perform exclusive measurements of direct reactions with the radioactive beams from the SPIRAL1 facility. The performance of the set-up is described through its commissioning and two examples of transfer reactions measured during the campaign. High accuracy spectroscopy of the nuclei of interest, including cross-sections and angular distributions, is achieved through the triple-coincidence measurement. In addition, the correction from Doppler effect of the γ-ray energies is improved by the detection of the light particles and the use of two-body kinematics and a full rejection of the background contributions is obtained through the identification of heavy residues. Moreover, the system can handle high intensity beams (up to 108 pps). The particle identification based on the measurement of the time-of-flight between MUGAST and VAMOS and the reconstruction of the trajectories is investigated.noneAssie M.; Clement E.; Lemasson A.; Ramos D.; Raggio A.; Zanon I.; Galtarossa F.; Lenain C.; Casal J.; Flavigny F.; Matta A.; Mengoni D.; Beaumel D.; Blumenfeld Y.; Borcea R.; Brugnara D.; Catford W.; de Oliveira F.; Delaunay F.; De Sereville N.; Didierjean F.; Diget C.A.; Dudouet J.; Fernandez-Dominguez B.; Fougeres C.; Fremont G.; Girard-Alcindor V.; Giret A.; Goasduff A.; Gottardo A.; Goupil J.; Hammache F.; John P.R.; Korichi A.; Lalanne L.; Leblond S.; Lefevre A.; Legruel F.; Menager L.; Million B.; Nicolle C.; Noury F.; Rauly E.; Rezynkina K.; Rindel E.; Rojo J.S.; Siciliano M.; Stanoiu M.; Stefan I.; Vatrinet L.Assie, M.; Clement, E.; Lemasson, A.; Ramos, D.; Raggio, A.; Zanon, I.; Galtarossa, F.; Lenain, C.; Casal, J.; Flavigny, F.; Matta, A.; Mengoni, D.; Beaumel, D.; Blumenfeld, Y.; Borcea, R.; Brugnara, D.; Catford, W.; de Oliveira, F.; Delaunay, F.; De Sereville, N.; Didierjean, F.; Diget, C. A.; Dudouet, J.; Fernandez-Dominguez, B.; Fougeres, C.; Fremont, G.; Girard-Alcindor, V.; Giret, A.; Goasduff, A.; Gottardo, A.; Goupil, J.; Hammache, F.; John, P. R.; Korichi, A.; Lalanne, L.; Leblond, S.; Lefevre, A.; Legruel, F.; Menager, L.; Million, B.; Nicolle, C.; Noury, F.; Rauly, E.; Rezynkina, K.; Rindel, E.; Rojo, J. S.; Siciliano, M.; Stanoiu, M.; Stefan, I.; Vatrinet, L