Publications by authors named "Ian C Metcalfe"

Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease.

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The proliferation of influenza viruses causes costly, recurrent, annual epidemics. Current vaccines, mainly administered parenterally, have been shown to be suboptimal in terms of efficacy, particularly where local IgA responses are concerned. Recent investigations of virosomes as delivery systems for viral HA and NA antigens have demonstrated an improved immune response.

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Immunopotentiating reconstituted influenza virosomes possess several characteristics defining them as vaccine adjuvants. Virosomes have been shown to provide vaccine components with protection from extracellular degradation; a regular, repetitive antigen structure aiding presentation to B lymphocytes and fully functional, fusion-active, influenza haemagglutinin envelope proteins that enables receptor-mediated uptake and intracellular processing of the antigen. In addition, virosomes, as vaccine delivery systems, have been shown to be safe and not to engender any antibodies against the phospholipid components.

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Conventional influenza vaccines currently in use are administered parenterally and generally confer good protection against systemic disease through the induction of high titers of serum virus-neutralizing antibodies. Parenteral vaccines are suboptimal in that they fail to induce a local mucosal response that may prevent the early stages of virus infection. Thus, the intranasal administration of a vaccine may provide a viable alternative to the parenteral route.

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The development of novel and increasingly safer vaccines frequently utilizes well-characterized antigens, in particular highly purified proteins or synthetic peptides. In spite of some achievements, this approach is frequently impeded by the fact that such antigens are often poor immunogens when administered alone. This fact has necessitated the development of suitable adjuvants that possess the ability to enhance the immunogenicity of a given antigen, preferably with little or no side effects.

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Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop vaccination strategies that lead to mucosal immune responses. Ideally, a vaccine should be administered mucosally in order to elicit mucosal protection.

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The use of vaccines for the prophylaxis of influenza in children is limited. This is despite high annual rates of influenza in children and despite the complications caused by influenza in children with chronic respiratory illnesses. The disease burden of influenza on infants and young children is reviewed and the potential of recommended influenza vaccination in healthy children, to reduce the direct and indirect health and socio-economic costs, is considered.

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Inflexal V, a novel virosome-based trivalent influenza vaccine, has been shown to be highly immunogenic and well tolerated in children, young adults, and the elderly. Here we discuss the techniques for the manufacture of Inflexal V, highlighting the purity and consistency of the manufacturing process. Key factors to be taken into account in the construction of Inflexal V are the retention of the natural presentation of antigens, its biodegradability and the presentation of few adverse events.

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