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(1)

The handle

http://hdl.handle.net/1887/74049

holds various files of this Leiden University

dissertation.

Author: Schipper, P.

(2)

Towards Controlled

Microneedle-Mediated

Intradermal Immunization

(3)

Cover design by Pim Schipper, Chris Hansler and Gerrit Riezebos. Layout design by Ilse Modder, www.ilsemodder.nl

Printed by Gildeprint Enschede, www.gildeprint.nl.

(4)

Towards Controlled

Microneedle-Mediated

Intradermal Immunization

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 donderdag 20 juni 2019

klokke 13.45 uur

door

Pim Schipper

Geboren op 22 december 1985

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TABLE OF CONTENTS

Chapter 1 9

General introduction Aim and outline of this thesis Chapter 2

Determination of depth-dependent intradermal immunogenicity of adjuvanted inactivated polio vaccine delivered by microinjections via hollow microneedles

27

Chapter 3

Antigen uptake by skin dendritic cells as function of antigen dose and intradermal injection depth

53

Chapter 4

Repeated fractional intradermal dosing of an inactivated polio vaccine by a single hollow microneedle leads to superior immune responses

83

Chapter 5

Diphtheria toxoid and N-trimethyl chitosan layer-by-layer coated pH-sensitive microneedles induce potent immune responses upon dermal vaccination in mice

105

Chapter 6

Chemical modifications of gold surfaces with basic groups and a fluorescent nanoparticle adhesion assay to determine their surface pKa

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