Chimeric proteins

Most conventional vaccines consist of killed organisms or purified antigemc components of pathogens. However, this approach of vaccine development has several limitations. Large-scale growth of pathogens may be difficult to achieve and is not completely free of risk. Furthermore, purification of relevant antigenic components from such pathogens may be expensive and time-consuming. Another approach is the use of synthetic peptides corresponding to immunogenic epitopes of pathogens. However, peptides are not immunogenic by themselves and need to be coupled to a carrier (see Chapter 6 ). Recent developments in molecular biology have opened up new possibilities for the production of vaccines and serum diagnostics. Protein antigens derived from pathogens can be expressed in attenuated bacteria, such as Salmonella aroA mutants (1 and see Chapter 4 ), which can be used as live oral vaccines. Such Salmonella strains have been shown to induce humoral, cellular, and mucosal immune responses in animals and humans (2-4). High-level expression of foreign antigens can be achieved in Salmonella using strong promoters (5). However, high-level expression of heterologous proteins can be deleterious or even lethal to bacteria. On the other hand, the foreign proteins may be rapidly degraded in the heterologous host. It might be more convenient, therefore, to create chimeric proteins by inserting well-defined epitopes of antigens derived from pathogens into bacterial carrier proteins, which can be expressed at high levels.