Examples of viral vector candidate vaccines in clinical development are listed in Table 6.3. Non-pathogenic

bacterial vectors have many features that make them an attractive vaccine platform. Bacterial vectors can be engineered for maximum safety (eg deletion of two or more genes from the same metabolic pathway), and to express large numbers of foreign antigens (Figure 6.5). Two key issues affecting bacterial vaccine vectors are: a) to decide whether the optimal platform should be a bacterial vaccine in its own right or a bacterial vector system to deliver exogenous EPZ5676 mouse antigens; and b) to determine whether re-administration of the vector, either with the same or different target antigens, will fail because of the immune response to the bacterial vector vaccine at the time of its initial administration.

Initial assessments of the feasibility of using attenuated bacterial vectors for the delivery of foreign antigens have focused on Salmonella species. Bacterial vaccine vectors for humans, however, have been disappointing so far. It may be necessary to develop unique Vincristine in vitro bacterial vaccine vectors for delivering exogenous antigens, in which case the vectors can be modified to allow for re-use. For example, if immunity against the vector, which is a major impediment to vaccine re-use, is determined by antibodies against the surface structures of the bacterium (such as lipopolysaccharide [LPS]), the dedicated vaccine vector could be developed to lack expression Progesterone of LPS or to express truncated/different forms of LPS to the target, thereby avoiding priming of the immune response and allowing for re-use of the vector and/or vaccine. Some potential options for live, attenuated

bacterial vectors are shown in Table 6.4. DNA vaccines are the result of the discovery in the early 1990s that the gene, rather than the encoded protein, if delivered in an ‘expressible’ form, could induce an immune response (see Chapter 1 – Vaccine evolution). The principle behind DNA vaccines is that the antigenic molecule is produced within the host from the DNA or RNA that is injected, in contrast to more traditional vaccination where the antigen is supplied in the vaccine formulation. The gene(s) for target antigen(s) is/are usually encoded in a circular plasmid expression vector under the control of promoter sequences that direct gene expression in mammalian cells, which is achieved after injection into mammals. The DNA vaccine process can circumvent some of the major issues resulting from recombinant protein administration.