This Article Full Text Full Text (PDF) Other Versions of this Article: CVI.00278-07v1 15/2/308    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Epaulard, O. Articles by Toussaint, B. Search for Related Content PubMed PubMed Citation Articles by Epaulard, O. Articles by Toussaint, B.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, February 2008, p. 308-313, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00278-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Optimization of a Type III Secretion System-Based Pseudomonas aeruginosa Live Vector for Antigen Delivery

TIMC-TheREx (UMR5525 CNRS-UJF), Bâtiment Jean Roget, 8th Floor, UFR de Médecine, Université Joseph Fourier Grenoble 1, 38706 La Tronche Cedex, France

Received 19 June 2007/ Returned for modification 1 November 2007/ Accepted 30 November 2007

During the last few years, the use of type III secretion system-based bacterial vectors for immunotherapy purposes has been assessed in various applications. We showed that a type III secretion-based Pseudomonas aeruginosa vector delivering the ovalbumin (OVA) antigen induced an efficient specific CD8⁺ T-lymphocyte immune response against OVA-expressing cells. Because of the intrinsic toxicity of the vector, further virulence attenuation was needed. Therefore, we explored the effects of the deletion of quorum-sensing genes and the aroA gene toward toxicity and efficiency of the vector strain. The aroA mutation in our strain (making the strain auxotrophic for aromatic amino acids) conferred a strikingly reduced toxicity, with the bacterial lethal dose being more than 100 times higher than that of the parental strain. The quorum-sensing gene mutation alone was associated with a slightly reduced toxicity. In a prophylactic OVA-expressing melanoma mouse model, an OVA-delivering aroA-deficient mutant was the most efficient at a low dose (10⁵), but dose enhancement was not associated with a greater immune response. The quorum-sensing-deficient strain was the most efficient at a mild dose (10⁶), but this dose was close to the toxic dose. Combination of both mutations conferred the highest efficiency at an elevated dose (10⁷), in agreement with the known negative effects of quorum-sensing molecules upon T-cell activation. In conclusion, we have obtained a promising immunotherapy vector regarding toxicity and efficiency for further developments in both antitumor and anti-infectious strategies.

Published ahead of print on 19 December 2007.

This article has been cited by other articles:

• Derouazi, M., Toussaint, B., Quenee, L., Epaulard, O., Guillaume, M., Marlu, R., Polack, B. (2008). High-Yield Production of Secreted Active Proteins by the Pseudomonas aeruginosa Type III Secretion System. Appl. Environ. Microbiol. 74: 3601-3604 [Abstract] [Full Text]