HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges

Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials

N-acetylcysteine reduces oxidative stress in sickle cell patients

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ0-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling