Vivotif® – A ‘Magic Shield’ for Protection against Typhoid Fever and Delivery of Heterologous Antigens

Abstract

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.

Towards a human oral vaccine for anthrax: The utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy

“…Indeed, an attenuated Salmonella enterica serovar Typhi ( S . Typhi) strain, Ty21a, is currently licensed for use in humans as an oral vaccine against typhoid fever [10;11]. The feasibility of employing attenuated strains of Salmonella such as S .…”

Improvement of the live vaccine strain Salmonella enterica serovar Typhi Ty21a for antigen delivery via the hemolysin secretion system of Escherichia coli

“…However, several preclinical studies have shown that surface display or secretion are more suitable for heterologous antigen delivery by attenuated Salmonella strains (Gentschev et al, 2002b;Hess et al, 1996;Ru¨ssmann et al, 1998;Spreng et al, 2003) than the cytoplasmic expression employed in the above-mentioned clinical trials (Bumann et al, 2001;Metzger et al, 2004). Therefore, we recently assessed the E. coli hemolysin secretion system for the delivery of heterologous antigens by Ty21a (Gentschev et al, 2004(Gentschev et al, , 2007. We have chosen the hemolysin secretion system because it has been used in numerous preclinical studies for the delivery of antigens from bacteria, viruses, and parasites by attenuated Salmonella strains (Gentschev et al, 2002a) as well as in the immunotherapy of tumors (Fensterle et al, 2008;Gentschev et al, 2005), as a delivery system for immunocontraceptive vaccines (Donner et al, 1998), and as a system for the coexpression and co-delivery of active cytokines (Hahn et al, 1998).…”

Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B

“…This is the first example demonstrating that the T1SS is a versatile tool for the delivery of a combination of cancer antigens with CtxB in S. enterica serovar Typhimurium. Moreover, we have recently shown that this secretion system is also fully active in S. enterica serovar typhi Ty21a, 49,50 the only Salmonella vaccine strain registered for human use. 51 In addition S. typhi Ty21a can efficiently secrete this CtxB-PSA-HlyAs protein (Gentschev et al, in preparation).…”