Background. It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)–1 vaccine. We assessed T-cell response markers ...as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial. Methods. 2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4+ T-cell magnitude and Envspecific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection. Results. We observed an unexpectedly strong inverse correlation between Env-specific CD8+ immune response magnitude and HIV-1 infection risk (hazard ratio HR = 0.18 per SD increment; P = .04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01). Conclusions. Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection.
This paper presents the design of an intelligent delivery engine (IDE) to facilitate the construction and consumption of learning virtual objects (LVOs) in complex, large-scale cooperative eLearning ...environments (CeLEnv). The research work brings four main contributions to knowledge: a) our current explorations into AI and eLearning; b) the definition of a top-down CeLEnv analysis methodology; c) the design of LVO structures; and d) the design of the IDE-LVO architecture. The IDE serves to dynamically deliver LVOs using a special registry of structures. Basic, composite and cooperative LVOs can be created and registered using the CeLEnv methodology. The IDE delivers all these objects to either software platforms or final users, according to some CeLEnv specifications. The paper describes the core elements of the CeLEnv methodology and, the high level design of the IDE
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