Vaccines against typhoid fever.

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. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine.

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. This paper investigates the efficacy of a novel virosome-based intranasal influenza vaccine by its ability to reduce disease symptoms and its effect on viral shedding in nasal secretions of immunised ferrets. The use of ferrets in the study of influenza vaccines is based on the good comparability between ferret and human response to the disease. Intranasal, as opposed to parenteral, administration of a trivalent virosome-based subunit vaccine adjuvanted with HLT provides an almost total prevention of virus shedding combined with a high level of immunological protection against homologous virus challenge. The ease of application of an intranasal vaccine may have positive repercussions in the adoption of influenza vaccinations, particularly in 'at-risk' groups.

Influenza virosomes as an efficient system for adjuvanted vaccine delivery.

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. Through the use of virosomes as a delivery vehicle, a number of vaccines have been developed. In humans, virosome-based vaccines containing inactivated hepatitis A and influenza antigens have been found to be efficacious and well-tolerated and have been on the market for several years. Hepatitis B, nucleic acids, cytotoxic drugs, and tetanus and diphtheria toxoids have also been incorporated into virosomes. Further investigations are ongoing in order to define the full potential of virosomes in both prophylactic and immunotherapeutic applications.

Virosomal adjuvanted antigen delivery systems.

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. This paper discusses one of the successes of vaccinology of the past decade: virosomal vaccines. The principles of the concept, immunoadjuvant action and application of virosomes in two currently licensed vaccines are detailed, with specific reference to the induction of both humoral and cellular immunity.

Nonclinical safety evaluation of Escherichia coli heat-labile toxin mucosal adjuvant as a component of a nasal influenza vaccine.

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. Indeed, intranasal administration of vaccine antigens when formulated with an appropriate mucosal adjuvant (e.g., bacterial toxins), results in a vigorous local and systemic immune response. This review discusses the nonclinical safety evaluation of Escherichia coli heat-labile toxin as a mucosal adjuvant for an intranasally administered influenza vaccine.

Experience with registered mucosal vaccines.

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. Several attenuated live viral and bacterial pathogens are registered as oral vaccines for human use, including the oral polio vaccine (Sabin) as well as attenuated strains of Salmonella typhi and Vibrio cholerae. These attenuated bacterial live vaccines-S. typhi Ty21a as well as V. cholerae CVD 103-HgR-are employed as vaccines against typhoid and cholera, respectively. In this manuscript, we review the immune responses that are induced by these vaccines, with a focus on mucosal immunity.

Inflexal V a trivalent virosome subunit influenza vaccine: production.

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. The constituents of the vaccine were also carefully considered based on suitability for human use, adjuvanticity and an innate lack of toxicity.

Virosome influenza vaccine in children.

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. Clinical experience with a virosome-formulated subunit influenza vaccine in children is presented. These clinical trials in children have shown a virosome-formulated subunit influenza vaccine to be immunogenic and well tolerated, indicating that it might be recommended for immunising healthy infants and children against influenza virus.