The Lancet infectious diseases
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Randomized Controlled Trial Multicenter Study
Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study.
Replication-competent virus vector vaccines might have advantages compared with non-replicating vector vaccines. We tested the safety and immunogenicity of an oral adenovirus serotype 4 vector vaccine candidate (Ad4-H5-Vtn) expressing the haemagglutinin from an avian influenza A H5N1 virus. ⋯ Wellcome Trust Foundation, PaxVax.
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Review
Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach.
Failures of highly touted trials have caused experts to call for re-evaluation of the current approach toward sepsis. New research has revealed key pathogenic mechanisms; autopsy results have shown that most patients admitted to intensive care units for treatment of sepsis had unresolved septic foci at post mortem, suggesting that patients were unable to eradicate invading pathogens and were more susceptible to nosocomial organisms, or both. These results suggest that therapies that improve host immunity might increase survival. ⋯ Collectively, these studies emphasise the degree of immunosuppression that occurs in sepsis, and explain why many previous sepsis trials which were directed at blocking inflammatory mediators or pathogen recognition signalling pathways failed. Finally, highly encouraging results from use of the new immunomodulatory molecules interleukin 7 and anti-programmed cell death 1 in infectious disease point the way for possible use in sepsis. We hypothesise that immunoadjuvant therapy represents the next major advance in sepsis.
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To bring new antibacterial drugs to the market is challenging because discovery of new agents is difficult, two large trials per indication are needed in accordance with traditional regulatory requirements, and the economic reward is limited if the use of new antibiotics is constrained. These challenges have resulted in an alarmingly thin antibiotic pipeline, despite the rapid and continued growth in the need for new drugs. ⋯ Therefore, a tiered regulatory framework that allows either disease-based or pathogen-based label indications is proposed, with label wording that promotes the most appropriate use of new agents. Such a framework is within the bounds of present regulatory approaches, is amenable to international harmonisation, and would be a welcome step towards the facilitation of a robust and sustainable discovery and development infrastructure.