Use of the α-hemolysin secretion system of Escherichia coli for antigen delivery in the Salmonella typhi Ty21a vaccine strain

Gentschev, Ivaylo; Dietrich, Guido; Spreng, Simone; Neuhaus, Beatrice; Maier, Elke; Benz, Roland; Goebel, Werner; Fensterle, Joachim; Rapp, Ulf R.

doi:10.1016/j.ijmm.2004.07.010

Cited by 15 publications

(15 citation statements)

References 33 publications

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“…doses (10 9 CFU for Ty21a and CVD908-htrA and 10 7 CFU for Ty800 recombinant strains), with the first dose given on day 1 and the second dose given 1 month later. The 10 9 -CFU doses and schedule were chosen according to previously reported experiments performed by other groups using the nasal murine model with Ty21a (16,23) and CVD908-htrA (27). Administration of Ty800 to mice was not previously reported.…”

Section: Resultsmentioning

confidence: 99%

“…There have been limited investigations of the use of Ty21a as a carrier for heterologous proteins. The induction of specific antibody responses by Ty21a expressing surface-displayed viral antigens (23) or hemolysin (16) was reported in the mouse nasal model, while no humoral response but some specific T-cell responses were reported after oral vaccination of human volunteers with Ty21a expressing H. pylori urease (9,30).…”

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confidence: 99%

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Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

Fraillery

Baud

Pang

et al. 2007

Clin Vaccine Immunol

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Human papillomavirus (HPV) vaccines based on L1 virus-like particles (VLPs) can prevent HPV-induced genital neoplasias, the precursors of cervical cancer. However, most cervical cancers occur in developing countries, where the implementation of expensive vaccines requiring multiple injections will be difficult. A live Salmonella-based vaccine could be a lower-cost alternative. We previously demonstrated that high HPV type 16 (HPV16)-neutralizing titers are induced after a single oral immunization of mice with attenuated Salmonella enterica serovar Typhimurium strains expressing a codon-optimized version of HPV16 L1 (L1S). To allow the testing of this type of vaccine in women, we constructed a new L1-expressing plasmid, kanL1S, and tested kanL1S recombinants of three Salmonella enterica serovar Typhi vaccine strains shown to be safe in humans, i.e., Ty21a, the actual licensed typhoid vaccine, and two highly immunogenic typhoid vaccine candidates, Ty800 and CVD908-htrA. In an intranasal mouse model of Salmonella serovar Typhi infection, Ty21a kanL1S was unique in inducing HPV16-neutralizing antibodies in serum and genital secretions, while anti-Salmonella responses were similar to those against the parental Ty21a vaccine. Electron microscopy examination of Ty21a kanL1S lysates showed that L1 assembled in capsomers and capsomer aggregates but not well-ordered VLPs. Comparison to the neutralizing antibody response induced by purified HPV16 L1 VLP immunizations in mice suggests that Ty21a kanL1S may be an effective prophylactic HPV vaccine. Ty21a has been widely used against typhoid fever in humans with a remarkable safety record. These finds encourage clinical testing of Ty21a kanL1S as a combined typhoid fever/cervical cancer vaccine with the potential for worldwide application.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

Fraillery

Baud

Pang

et al. 2007

Clin Vaccine Immunol

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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Prostate cancer is the most common malignant tumor in men and is normally associated with increased serum levels of prostatespecific antigen (PSA). Therefore, PSA is one potential target for a prostate cancer vaccine. In this study we analyzed the functionality of new bacterial PSA vaccines, expressed and secreted via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of Type I secretion systems (T1SS) using an attenuated Salmonella enterica serovar Typhimurium aroA strain as carrier. The data demonstrate that a bacterial live vaccine encompassing T1SS in combination with cholera toxin subunit B can be successfully used for delivery of PSA to induce cytotoxic CD8 þ T-cell responses resulting in an efficient prevention of tumor growth in mice.

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“…In our recent study, S. typhi Ty21a carrying a haemolysin expression vector was grown, harvested, lyophilised and formulated on a pilot scale using the same raw materials and production procedures used for commercial production of the registered Vivotif vaccine. Under these conditions, episomal HlyA expression vectors, stably replicated in Ty21a in vitro and in vivo, and haemolysin were efficiently expressed and secreted by the vaccine strain after formulation according to the procedure licensed for Vivotif production [39] . We also demonstrated stress stability (at 15, 25 and 37 ° C) and short-term stability at the registered storage temperature (2-8 ° C) of bacterial counts, plasmid maintenance and antigen expression.…”

Section: Delivery Of Heterologous Antigens By Ty21amentioning

confidence: 99%

“…Furthermore, we performed immunisation studies by intranasal immunisation of mice, since the intranasal mouse model is the most suitable animal model available today [2] . Furthermore, Ty21a maintains the haemolysin expression vector after immunisation of mice and that intranasal immunisation of mice with Ty21a secreting HlyA results in strong IgG responses against the heterologous antigen [39] . Hence, the well-established commercial formulation of the Vivotif vaccine is also suitable for the production of Ty21a carrying heterologous antigens, and recombinant Ty21a strains may form the basis for a novel generation of combination vaccines which can be administered orally.…”

Section: Delivery Of Heterologous Antigens By Ty21amentioning

confidence: 99%

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

Gentschev¹,

Spreng²,

Sieber³

et al. 2007

Chemotherapy

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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.

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Use of the α-hemolysin secretion system of Escherichia coli for antigen delivery in the Salmonella typhi Ty21a vaccine strain

Cited by 15 publications

References 33 publications

Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

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

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

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