Promotor: W. Jiskoot, Co-promotor: A. Kros

Tuberculosis is a major global health problem caused by the Mycobacterium tuberculosis complex, claiming more than a million lives annually.

Promotores: Prof.dr. J. A. Bouwstra, Prof.dr. W. Jiskoot

The research described in this Thesis was aimed at designing and synthesizing nature-inspired compounds as part of TB vaccine discovery.

This thesis investigates innovative and classical strategies in glycoconjugate vaccine development to address the growing threat of multidrug-resistant bacterial infections.

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

Promotores: Wim Jiskoot; Ferry Ossendorp

Promotores: Prof.dr. G.F.A Kersten, Prof dr. J.A. Bouwstra

The chemical and structural heterogeneity of toxoid vaccines makes their analysis challenging. However, detailed insights on a molecular level can be obtained by mass spectrometry.

This thesis describes the development of improved formulations and alternative delivery strategies for polio vaccination.

The intradermal administration route is attractive for vaccine delivery, because of the highly populated antigen-presenting cells in the skin. However, the skin’s main physical barrier, the stratum corneum, prevents vaccines from entering the skin.

Promotores: Prof.dr. G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Promotores: W. Jiskoot, F. Ossendorp

Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein.

In this article, Dimiter Toshkov investigates the determinants of COVID-19 vaccine hesitancy and refusal, focusing on Eastern, Southern and Western Europe.

Nanoparticles can be used as delivery systems for both small molecules and macromolecules such as proteins, peptides or oligonucleotides. This thesis focuses on the use of liposomes, nanometric vesicles formed by a lipid bilayer enclosing an aqueous core. Liposomes are highly versatile delivery syst…

Lipid nanoparticles (LNPs) have enabled the success of mRNA vaccines but remain limited in broader therapeutic use by challenges in delivery efficiency, targeting, and mechanistic understanding.

Bulgarije kwam relatief ongeschonden uit de eerste golf, maar in het najaar van 2020 namen het aantal infecties, ziekenhuisopnames en sterfgevallen sterk toe. Dit onderzoek analyseert hoe de Bulgaarse regering op de Covid-19 pandemie heeft gereageerd.

In this article, Dimiter Toshkov aims to explains the gender gap in COVID-19 vaccination attitudes.

The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide.

Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.

This dissertation presents the synthesis and evaluation of antibody recognition for various capsular polysaccharide (CP) fragments of Staphylococcus aureus (S. aureus).

This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

This dissertation explores new chemical strategies for the synthesis of self-adjuvanting peptide conjugates and immunomodulatory ligands aimed at targeted activation of the immune system.

Promotor: Prof.dr. G.A. van der Marel, Co-Promotor: J.D.C. Codée

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

Nanodiscs are small, disc-shaped structures designed to mimic biological cell membranes, composed of a lipid bilayer stabilized by scaffold proteins. Membrane proteins play crucial roles in essential processes such as nutrient and waste transport, molecular recognition, and cell signalling, making them…

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

The aim of this thesis was to develop aluminium salt-based nanoparticles that may ultimately be used as adjuvant in human vaccines.

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Carbohydrates are present on the surface of bacteria making them suitable antigen candidates for vaccine development. This thesis deals with the synthesis of two carbohydrate-based components; the capsular polisaccharide of S. aureus type 5 and teichoic acids from staphilococci and enterococci speci…

Leidse chemici maakten in het lab de bacteriële capsule van meningokokken na. Met een paar aanpassingen kunnen deze capsules dienen als extra veilig en effectief vaccin tegen deze beruchte bacteriën, die onder andere hersenvliesontsteking kunnen veroorzaken. Promovendus Jacopo Enotarpi en zijn team…

Promotor: G.A. van der Marel, Co-promotor: D.C. Codée

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades.

Schistosomiasis is an acute and chronic disease caused by blood dwelling parasitic trematodes of the genus Schistosoma, and it is classified as the second most socioeconomically devastating parasitic disease, second only to malaria.

One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response.

In order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course.Unravelling the fundamental molecular mechanisms influencing the onset and course of diseases such as allergies,…

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates.

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