DNA vaccine encoding endosome-targeted human papillomavirus type16 E7protein generates CD4+ T cell-dependent protection

• Published in: European Journal of Immunology 2007-02, Vol.37 (2), p.376-384
• Main Authors: Brulet, Jean-Marc, Maudoux, Frederic, Thomas, Severine, Thielemans, Kris, Burny, Arsene, Leo, Oberdan, Bex, Francoise, Hallez, Sophie
• Format: Article
• Language: English
• Subjects: Human papillomavirus
• ISSN: 0014-2980; 1365-2567
• DOI: 10.1002/eji.200636233

Human papillomavirus type16 is commonly implicated in cervical cancers. The viral genome encodes potential targets like the oncoproteinE7, expressed in transformed cells but thought to represent a poorly immunogenic antigen. We describe in this work a DNA-based vaccination protocol aimed at inducing an efficient anti-E7 immune response in vivo. Plasmids allowing the expression of the E7protein in distinct cellular compartments were generated and assayed in an in vivo model of tumor growth. Our data demonstrate that mice vaccinated with a plasmid encoding for an E7protein fused to a domain of the MHC classII-associated invariant chain (IiE7) were protected against tumor challenge. Mice immunized against an ubiquitinated form of E7 (Ub(Ala)E7) failed to control tumor growth. Protection induced by IiE7 was correlated with the development of CD8+ CTL and required the presence of CD4+ cells. In vitro studies confirmed that the IiE7 fusion protein was expressed at high levels in the endosomal compartment of transfected cells, while the natural and the ubiquitin-modified form of E7 were mainly nuclear. The present study suggests that an efficient anti-tumor response can be induced in vivo by DNA constructs encoding for E7protein forms localizing at the endosomal compartment. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636233 .