Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.

OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. DESIGN: A randomized, observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⁺ cell counts below 200 cells/μl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals [interquartile range (IQR) CD4⁺ cell counts at screening: 438-872 cells/μl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⁺ cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⁺ T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40L⁺IL-2⁺TNF-α⁺, CD40L⁺IL-2⁺ and CD40L⁺IL-2⁺TNF-α⁺IFN-γ⁺]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.

New perspectives in the use of ink evidence in forensic science: Part I. Development of a quality assurance process for forensic ink analysis by HPTLC

The level of information provided by ink evidence to the criminal and civil justice system is limited. The limitations arise from the weakness of the interpretative framework currently used, as proposed in the ASTM 1422-05 and 1789-04 on ink analysis. It is proposed to use the likelihood ratio from the Bayes theorem to interpret ink evidence. Unfortunately, when considering the analytical practices, as defined in the ASTM standards on ink analysis, it appears that current ink analytical practices do not allow for the level of reproducibility and accuracy required by a probabilistic framework. Such framework relies on the evaluation of the statistics of the ink characteristics using an ink reference database and the objective measurement of similarities between ink samples. A complete research programme was designed to (a) develop a standard methodology for analysing ink samples in a more reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in a forensic context. This report focuses on the first of the three stages. A calibration process, based on a standard dye ladder, is proposed to improve the reproducibility of ink analysis by HPTLC, when these inks are analysed at different times and/or by different examiners. The impact of this process on the variability between the repetitive analyses of ink samples in various conditions is studied. The results show significant improvements in the reproducibility of ink analysis compared to traditional calibration methods.