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The following handle holds various files of this Leiden University dissertation:

http://hdl.handle.net/1887/59474

Author: Panagioti, E.

Title: Targeting and exploiting cytomegalovirus for vaccine development

Issue Date: 2017-12-05

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TARGETING AND EXPLOITING CYTOMEGALOVIRUS FOR VACCINE DEVELOPMENT

Proefschrift

ter verkrijging van 

de graad van Doctor aan de Universiteit Leiden,  op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het college voor Promoties te verdedigen op

dinsdag 5 december 2017 klokke 15:00 uur

door

Eleni Panagioti geboren te Athene in 1988

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The research described in this thesis was performed at the Departments of Medical Oncology and Immunohematology and Blood Transfusion of the Leiden University Medical Center, Leiden, The Netherlands and was funded by the EU under the FP7 Marie Curie Action VacTrain (Grant number: 316655). Financial support for the publication of this thesis was provided by the Leiden University Medical Center.

Cover Design: Eleni Panagioti & Botsas Design Studio. Inspired by Wassily Kandinsky’s colour studies and squares with concentric circles.

Layout & Printing: Off Page, Amsterdam

ISBN: 978-94-6182-855-2

Copyright © by 2017 E. Panagioti. All rights reserved. No part of this thesis may be reproduced in any form or by any means without permission of the author.

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PROMOTOR

Prof. dr. S. H. van der Burg 

CO-PROMOTOR

Dr. R. Arens 

LEDEN PROMOTIECOMMISSIE:

Dr. M. G. H. Betjes (Erasmus University Medical Center, Rotterdam) Prof. dr. A. Geluk

Prof. dr. E.J.H.J. Wiertz (University Medical Center Utrecht, Utrecht) Prof. dr. B.A. M. van der Zeijst

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TABLE OF CONTENTS

Chapter 1 General introduction 7

Chapter 2 The breadth of synthetic long peptide vaccine-induced CD8+ T cell 29 responses determines the efficacy against mouse cytomegalovirus infection Chapter 3 Enforced OX40 stimulation empowers booster vaccines to 59

induce effective CD4+ and CD8+ T cell responses against mouse cytomegalovirus infection

Appendix to chapter 3 91

Chapter 4 The spontaneous response to Human Cytomegalovirus immediate early 99 protein 2 is focused on 5 highly immunogenic regions and predominantly comprises polyfunctional type 1 CD4+ T cells

Chapter 5 The level of pre-existing immunity determines the efficacy of 127 MCMV-based vaccine vectors

Chapter 6 Requirements for effective T cell-inducing vaccines against 147 chronic viral infections

Chapter 7 General Discussion 169

Chapter 8 Appendix 183

English summary 185

Nederlandse samenvatting 187

Abbreviations 189

Curriculum vitae 190

List of publications 191

Aknowledgements 192

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