MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans
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MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans. / Esposito, Ilaria; Cicconi, Paola; D'Alise, Anna Morena; Brown, Anthony; Esposito, Marialuisa; Swadling, Leo; Holst, Peter Johannes; Bassi, Maria Rosaria; Stornaiuolo, Mariano; Mori, Federica; Vassilev, Ventzislav; Li, Wenqin; Donnison, Timothy; Gentile, Chiara; Turner, Bethany; von Delft, Annette; Del Sorbo, Mariarosaria; Barra, Federica; Contino, Alessandra Maria; Abbate, Adele; Novellino, Ettore; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Lahm, Armin; Grazioli, Fabiana; Ammendola, Virginia; Siani, Loredana; Colloca, Stefano; Klenerman, Paul; Nicosia, Alfredo; Dorrell, Lucy; Folgori, Antonella; Capone, Stefania; Barnes, Eleanor; PEACHI Consortium.
In: Science Translational Medicine, Vol. 12, No. 548, eaaz7715, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans
AU - Esposito, Ilaria
AU - Cicconi, Paola
AU - D'Alise, Anna Morena
AU - Brown, Anthony
AU - Esposito, Marialuisa
AU - Swadling, Leo
AU - Holst, Peter Johannes
AU - Bassi, Maria Rosaria
AU - Stornaiuolo, Mariano
AU - Mori, Federica
AU - Vassilev, Ventzislav
AU - Li, Wenqin
AU - Donnison, Timothy
AU - Gentile, Chiara
AU - Turner, Bethany
AU - von Delft, Annette
AU - Del Sorbo, Mariarosaria
AU - Barra, Federica
AU - Contino, Alessandra Maria
AU - Abbate, Adele
AU - Novellino, Ettore
AU - Thomsen, Allan Randrup
AU - Christensen, Jan Pravsgaard
AU - Lahm, Armin
AU - Grazioli, Fabiana
AU - Ammendola, Virginia
AU - Siani, Loredana
AU - Colloca, Stefano
AU - Klenerman, Paul
AU - Nicosia, Alfredo
AU - Dorrell, Lucy
AU - Folgori, Antonella
AU - Capone, Stefania
AU - Barnes, Eleanor
AU - PEACHI Consortium
N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PY - 2020
Y1 - 2020
N2 - Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+CD8+ 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.
AB - Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+CD8+ 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.
U2 - 10.1126/scitranslmed.aaz7715
DO - 10.1126/scitranslmed.aaz7715
M3 - Journal article
C2 - 32554708
VL - 12
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 548
M1 - eaaz7715
ER -
ID: 243387581