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Vaccines against gut pathogens
  2. F BOWE,
  3. R CAHILL,
  1. Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
  1. Professor Gordon Dougan.

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Many infectious agents enter the body using the oral route and are able to establish infections in or through the gut. For protection against most pathogens we rely on immunity to prevent or limit infection. The expression of protective immunity in the gut is normally dependent both on local (mucosal) and systemic mechanisms. In order to obtain full protection against some pathogens, particularly non-invasive micro-organisms such as Vibrio cholerae, mucosal immunity may be particularly important. There is a need to take these factors into account when designing vaccines targeting gut pathogens. Conventional parenteral vaccines (injected vaccines) can induce a degree of systemic immunity but are generally poor stimulators of mucosal responses. Thus, a basic prerequisite for designing novel vaccines against gut associated pathogens may be the requirement to induce mucosal and potentially systemic immunity.1 The most effective way to induce local immunity against infectious agents has so far proved to be direct application of vaccine antigens to mucosal surfaces (oral or intranasal delivery).2 The fact that we have so few effective oral vaccines shows that the induction of protective immunity through oral immunisation is not an easy goal to achieve as many antigens are poor oral immunogens. Here we will focus, using bacterial pathogens as examples, on some recent approaches being used to generate novel oral vaccines.

Live vaccines

Oral vaccines can be based on either live or non-living antigens. The generation of modern live oral vaccines involves the construction of genetically defined attenuated micro-organisms capable of inducing immunity in a non-harmful way. The recent improved understanding of bacterial virulence associated gene function offers the possibility of introducing multiple, defined, attenuating and stable mutations into the genome of bacterial pathogens. Furthermore, the use of precisely attenuated bacterial vectors as carriers for recombinant heterologous antigens can lead to the generation of …

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