Vivotif--a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens.

The attenuated Salmonella typhi strain Ty21a is the main constituent of Vivotif, the only attenuated live oral vaccine against typhoid fever. In comparison with antibiotics, the 'magic bullets' which Paul Ehrlich was striving for to treat infectious diseases, this vaccine should be viewed as a 'magic shield', because rather than treating typhoid fever after the infection has started, immunisation with this vaccine strain prevents infection and disease by the induction of specific immune responses. Ty21a is also an attractive carrier for the delivery of heterologous antigens. Recently, we successfully used Ty21a for antigen delivery via the haemolysin secretion system of Escherichia coli, which allows efficient protein secretion from the carrier bacteria.

Vaccines against typhoid fever.

Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.