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Infection and Immunity, December 2002, p. 7114-7119, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7114-7119.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Concomitant Cytosolic Delivery of Two Immunodominant Listerial Antigens by Salmonella enterica Serovar Typhimurium Confers Superior Protection against Murine Listeriosis

Emeka I. Igwe,1 Gernot Geginat,2 and Holger Rüssmann1*

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität München, 80336 Munich,1 Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, 68167 Mannheim, Germany2

Received 13 June 2002/ Returned for modification 20 July 2002/ Accepted 20 August 2002

During its interaction with host cells, Salmonella enterica serovar Typhimurium employs a type III secretion system for cytosolic targeting of virulence factors. This protein translocation mechanism is a useful tool for heterologous antigen delivery by attenuated Salmonella vaccine carrier strains. In the present study, we used the Yersinia outer protein E (YopE) as a carrier molecule for Salmonella type III-dependent cytosolic delivery of the immunodominant CD8 T-cell antigens listeriolysin O (LLO) and p60 of Listeria monocytogenes. It is shown that concomitant translocation of hybrid YopE/LLO and YopE/p60 proteins by Salmonella led to antigen presentation and CD8 T-cell priming efficacies comparable to those of translocation of single listerial antigens. However, simultaneous translocation of LLO and p60 significantly surpassed single cytosolic antigen delivery in the ability to protect against Listeria. For the first time, this study demonstrates that concomitant expression of two independent antigens via the same recombinant plasmid leads to superior protection against a challenge with an intracellular bacterial pathogen. In conclusion, these findings emphasize the versatility of Salmonella type III-mediated heterologous antigen delivery for the induction of cytotoxic T-lymphocyte-mediated immunity.

* Corresponding author. Mailing address: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität München, Pettenkoferstr. 9a, 80336 Munich, Germany. Phone: 49-89-51605261. Fax: 49-89-51605248. E-mail: ruessmann{at}m3401.mpk.med.uni-muenchen.de.

Editor: J. T. Barbieri

Infection and Immunity, December 2002, p. 7114-7119, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7114-7119.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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