MHC class II invariant chain–adjuvanted viral vectored vaccines enhances T cell responses in humans
Ilaria Esposito, Paola Cicconi, Anna Morena D’Alise, Anthony Brown, Marialuisa Esposito, Leo Swadling, Peter Johannes Holst, Maria Rosaria Bassi, Mariano Stornaiuolo, Federica Mori, Ventzislav Vassilev, Wenqin Li, Timothy Donnison, Chiara Gentile, Bethany Turner, Annette von Delft, Mariarosaria Del Sorbo, Federica Barra, Alessandra M. Contino, Adele Abbate, Ettore Novellino, Allan Randrup Thomsen, Jan Pravsgaard Christensen, Armin Lahm, Fabiana Grazioli, Virginia Ammendola, Loredana Siani, Stefano Colloca, Paul Klenerman, A Nicosia, Lucy Dorrell, Antonella Folgori, Stefania Capone, Eleanor Barnes, Carly M. Bliss, Emma Ghaffari, Felicity Hartnell, Jakub Kopycinski, Shokouh Makvandi‐Nejad, Verity Nevin, Dorota Borys, Dominique Boutriau, Landry Cochard, Lan Lin, Frank Struyf, Tomáš Hanke, Ciarán Bannan, Colim Bergin, Matthias Hoffman, Patrick Schmid, Pietro Vernazza, Clair M. Gardiner, Elena Woods
Abstract
cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections.