Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer.

Infection of the cornea with herpes simplex virus (HSV) can result in a chronic disease called herpetic stromal keratitis (HSK). The disease represents one of the leading causes of infectious blindness in the Western world. Immune-mediated cellular damage is suspected in the pathogenesis of human HSK. The murine model has been pivotal in further establishing HSK as an immunopathological disease. This article reviews understanding of HSK, both in humans and in the mouse model, with an emphasis on possible future therapeutic strategies to counteract this blinding immunoinflammatory disease

Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.

Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicised isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection.

Asthma is a complex disorder in which major genetic and environmental factors interact to initiate the disease and propagate it as a chronic relapsing disorder. Until recently, genetic factors implicated in the disease pathogenesis have been restricted to variants in known molecules involved in the inflammatory or remodelling pathways. This review discusses evidence for a new susceptibility gene for asthma, ADAM33, which was identified by positional cloning and shown to be selectively expressed in mesenchymal but not immune or inflammatory cells. ADAM33 belongs to a family of membrane–anchored metalloproteinases that also have fusagenic, adhesion and intracellular signalling properties. ADAM33 might play a key role in predisposing to the reduced lung function characteristic of asthma, possibly by influencing airway wall remodelling.

Sepsis is an often-fatal response of the immune system against microbial pathogens. The molecular mechanisms that have been designed to protect the host from invading pathogens are responsible for the damage and injury. It is now widely known that this crucial response of the immune system is mediated by innate immunity, which employs a plethora of pattern recognition receptors that recognise motifs expressed by pathogens. A lack of knowledge of the mediators involved in innate recognition has led to unsuccessful attempts at designing effective therapeutic interventions for sepsis. However, in recent years, great leaps forward have been achieved in our knowledge of these mediators. In this review we attempt to unravel the molecular mechanisms underlying bacterial recognition, particularly recognition of bacterial lipopolysaccharide, and we propose future potential therapeutic targets for septic shock.