PhoE Protein as a Carrier for Foreign Epitopes

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Abstract
Most conventional vaccines consist of killed organisms or purified antigenic parts from these organisms. However this approach of vaccine development has several limitations. First, the large-scale growth of certain pathogenic organisms may be difficult to achieve and is not completely free of risk. Second, it may be difficult to establish whether a certain vaccine preparation is completely killed and free of contaminants. Furthermore, the purification of relevant antigenic parts may be time-consuming and expensive. A more sophisticated method is the use of synthetic peptides corresponding to immunogenic epitopes of pathogens for vaccination. However, such peptides are usually not immunogenic by themselves and therefore, they will have to be coupled to a carrier protein. Another approach is the use of viral carriers, like vaccinia, in which antigenic parts of pathogens can be expressed [1]. However, a serious drawback of this approach is that vaccination with such vectors may lead to disease in immunocompromised individuals. As an alternative for the viral vectors live attenuated bacteria, such as Salmonella aroA mutants [2], could be useful as an expression system for antigens, derived from potential pathogens. Such attenuated Salmonella strains have been shown to induce appropriate humoral, cellular and mucosal immune responses in both animal models and in humans [3, 4, 5]. After oral administration such bacteria can attach to and invade the gut-associated lymphoid tissues and persist for some time in their host. However because of well-defined, non-reverting attenuating mutations [5,6], these bacteria disappear from the host after a limited number of replications. An immune response of the host is not necessary for this process. It has been shown that oral administration of Salmonella gives better immune responses than injection with killed bacteria [7]. Attenuated Salmonella typhi strains are used to vaccinate humans against typhoid fever. Moreover, live attenuated Salmonella strains have been proven to be suitable for the delivery of foreign antigens to the immune system [8, 9]. Thus, such Salmonella strains seem to be a powerful means for raising immune responses, not only to Salmonella itself, but also to foreign proteins expressed in these strains.

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