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

Aluminium-based adjuvants, such as aluminium hydroxide and aluminium phosphate, are well-known for their immune-stimulating properties.

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

Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines,…

Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens.

For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…

Promotores: W. Jiskoot, F. Ossendorp

In the near future oral polio vaccine (OPV) will be replaced by inactivated polio vaccine (IPV) as part of the eradication program of polio. For that reason, there is a need for substantial amount of safe and more affordable IPV for low-income countries. Bioneedles, which are biodegradable mini-implants,…

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects…

Currently, several successful vaccines are available. However, for pathogens with a highly variable genetic composition, and for which serum IgG antibodies are not a useful correlate of protection, effective vaccines are yet to be developed.

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.

PhD Defence

PhD Defence

Promoter: J.G.E.M.Fraaije, Co-promotor: A. Kros

Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination.

The current hepatitis B vaccines need to be stored and transported under refrigerated conditions (2-8 degrees C). This dependence on a cold-chain is highly challenging in areas where hepatitis B virus infections are endemic.

PhD Defence

Microneedles are a promising tool for the painless administration of vaccines through the skin. But, are these minuscule needles really effective? PhD student Pim Schipper of the Leiden Academic Centre for Drug Research investigated various factors of vaccination via the skin and discovered, among other…

How are carbohydrates processed by the immune system? Can carbohydrates be used to trigger T-cells against other conjugated antigens? Can they be used as adjuvants?

Utilization of plant-originated products as new antibiotics

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery.

Atherosclerosis, in particular rupture of atherosclerotic plaques, is the underlying cause of most heart attacks or strokes and is the leading cause of death worldwide.

Bet v1, the major allergen in birch pollen, is one of the main causes of allergies such as asthma and rhino-conjunctivitis. Additionally it is the main cause of birch pollen allergy in humans.

Key publications of the Skin Barrier and Vaccination group.

The potential of liposomal cancer vaccines

PhD Defence

PhD Defence

PhD Defence

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC.

The loss of T-cell homeostasis and tolerance towards self-antigens is the underlying cause of autoimmune and inflammatory diseases like atherosclerosis, rheumatoid arthritis or type I diabetes. Traditionally, the treatment of these diseases consisted on systemic immune suppression, which can entail…

Source: Mediators Inflamm (2014)

Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis (TB), is the leader among all pathogens responsible for the most human deaths today and it is considered as one of the top 10 causes of death worldwide. There is an increasing occurrence of multidrug-resistant and even totally drug-resistant…

This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.

Vaccines are an extraordinary category of biopharmaceuticals. They are usually prophylactic and come in many types, from whole bacteria to peptides and nucleic acids. They are very cost effective and almost every human on the planet is vaccinated. The latter mandates that vaccines have to be extremely…

The Skin Barrier and Vaccination group is led by Prof. Joke Bouwstra. One of the key functions of the skin is its barrier function, which is located in the uppermost layer of the skin, the stratum corneum. The stratum corneum consists of enucleated dead cells (corneocytes) embedded in a lipid matrix.…

The research in the Biosyn group is focused on the design, synthesis and function of the four major types of biomolecules: nucleic acids, carbohydrates, peptides and lipids and hybrid structures thereof. These biomolecules and their derivatives are used in drug discovery and chemical biology, to develop…

Leiden researchers have carried out successful tests using a new method of packaging a cancer vaccine in nano-particles. The new vaccine has induced a strong immune reaction in mice. The researchers believe that this method can make an important contribution to the treatment of cancer. Their findings…

Current research at the Skin Barrier and Vaccination group.

Alexander Kros studies supramolecular systems in a biological environment. The unifying theme between the projects in my lab is specific molecular recognition, i.e. the intermolecular interaction between complementary molecules with high affinity and selectivity. Studying, imitating and dissecting processes…

Lecture