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Optimal epitope composition after antigen screening using a live bacterial delivery vector: Application to TRP-2

Madiha Derouazi, Yan Wang, Raphaël Marlu, Olivier Epaulard, Jean-François Mayol, Nicolas Pasqual, Audrey Le Gouellec, Benoit Polack and Bertrand Toussaint

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Immunotherapeutic approaches, based on the generation of tumor-specific cytotoxic T-lymphocytes (CTL), are currently emerging as promising strategies of anti-tumor therapy. The potential use of attenuated bacteria as engineered vectors for vaccine development offers several advantages, including the stimulation of innate immunity. We developed an attenuated live bacterial vector using the type III secretion system (TTSS) of Pseudomonas aeruginosa to deliver in vivo tumor antigens. Using an inducible and rapid expression plasmid, vaccination with several antigens of different length and epitope composition, including TRP-2, gp100 and MUC18, was evaluated against glioma tumor cells. We observed similar CTL immunity and T-cell receptor (TCR) repertoire diversity with the vaccines, TRP2125-243, TRP2L125-376 and TRP2S291-376. However, only immunization with TRP2L125-376 induced significant anti-tumor immunity. Taken together, our data indicate the importance of the epitopes composition and/or peptide length of these peptides for inducing cytotoxic T-lymphocyte (CTL) mediated immunity. Characteristics that consistently improved anti-tumor immunity include: long peptides with immunodominant and cryptic CD8+ epitopes, and strong CD4+ Th epitopes. Our bacterial vector is versatile, easy-to-use and quick to produce. This vector is suitable for rapide screening and evaluation of antigens of varying length and epitope composition.

Authors

Madiha Derouazi

University of Joseph Fourier; La Tronche, France

Yan Wang

University of Joseph Fourier; La Tronche, France

Raphaël Marlu

University of Joseph Fourier; La Tronche, France

Olivier Epaulard

University of Joseph Fourier; La Tronche, France

Jean-François Mayol

Centre de Recherches du Service de Santé des Armées; La Tronche, France

Nicolas Pasqual

ImmunIDtechnologies; Grenoble, France

Audrey Le Gouellec

University of Joseph Fourier; La Tronche, France

Benoit Polack

University of Joseph Fourier; La Tronche, France

Bertrand Toussaint Corresponding author: btoussaint@chu-grenoble.fr

University of Joseph Fourier; La Tronche, France

This is an open-access article

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.