ABSTRACT
Vaccination remains one of the most cost-effective methods of medical intervention in the battle to reduce human morbidity and mortality from infectious disease in the 21st century. However, its use remains limited due to the existence of many challenging scientific and ethical issues including the high cost of development and licensing, public acceptance of new technologies used in the generation of such vaccines, and high cost of litigation that may result from vaccine failure or damage. Yet the potential for worldwide protection and, in some cases such as smallpox, complete eradication of disease has driven scientists to consider the generation and development of new, effective, cheap, and easy to administer vaccines. To this end, vaccines that induce high levels of protection following a single immunization would be of great benefit, especially if they could be administered without the use of needles. In addition, it is thought that the stimulation of protective immune responses at the natural site of infection is necessary to achieve high levels of efficacy against some infectious agents. This may result in not only the protection of the individual, but also the reduction of the circulation of pathogens in the community and enhancement of herd immunity. For these and other related reasons, there has been a consistent and continuing interest in the development of vaccines that can be delivered via mucosal surfaces (particularly oral and nasal vaccines) [1]. However, the fact that so few mucosal vaccines are in current use indicates that there are significant barriers to their development. These include the fact that most soluble antigens are poorly immunogenic when delivered directly to the
host via mucosal surfaces. Even antigens such as tetanus toxoid that are potent immunogens when administered parenterally are weak mucosal immunogens [2]. Stimulation of such responses is limited, as although these surfaces have evolved to deal with the threat of microorganisms and their toxic products, protective immunity has to be induced without simultaneously mounting inappropriate immune responses to food and harmless environmental antigens. Hence there is a sophisticated network of immune regulation operating at the surfaces of the body that control immune responses in an antigen-specific manner [3-5]. Unfortunately, despite intensive investigation, these regulatory mechanisms are currently poorly understood. However, we have known for many years that live pathogens can act as mucosal immunogens, stimulating local and, in some cases, systemic immune responses during infection [6]. Using this information, attenuated derivatives of pathogens and their close relations have been created that can stimulate protective immunity without causing disease. Such live mucosal vaccines are considered elsewhere in this volume.
