Vaccination via the skin or the mucosae

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

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

Main challenges in skin vaccination are overcoming the stratum corneum (SC) barrier and targeting the antigen presenting cells (APC) in the epidermis and the dermis.

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.

Promotores: W. Jiskoot, F. Ossendorp

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

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,…

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.

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

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.

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.

Promotores: Wim Jiskoot; Ferry Ossendorp

The potential of liposomal cancer vaccines

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.

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

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.…

Atherosclerosis is a chronic inflammatory disease affecting millions of people world-wide.

The potential of bioneedles to deliver influenza vaccines was investigated.

Transcutaneous vaccination is attractive because it is non- or minimally invasive, pain free and the site of administration (skin) is easily accessible. What’s more, transcutaneous immunization can lead to a strong immune response owing to the presence of immune-competent cells in the skin.

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be…

Is there a sufficiently large market for drug screening and testing in Zebrafish larvae using membrane fusion?

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

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.

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

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,…

The Delivery of Biotherapeutics research group is led by Prof. Matthias Barz and focusses on the synthesis and characterization of polypept(o)ids and their application in nanomedicine to improve existing therapies or enable novel diagnostic or therapeutic approaches.

The aim of current study was to develop a dried inactivated polio vaccine (IPV) formulation with minimal loss during the drying process and improved stability when compared with the conventional liquid IPV.

Liposomes hold great promise for peptide-based personalized cancer vaccination, especially when administered intradermally. However, current liposome preparation methods are very time consuming (resulting in long development times per formulation), whereas personalized cancer vaccination requires very…

The objective is to develop in vitro antigen degradation assays in order to mimic the fate of the antigen in vivo.

On 11 March, pharmaceutical company Janssen received approval to launch its corona vaccine on the European market. This made Janssen the fourth company to be given the green light by the European Medicines Agency. As Lead of the Janssen Campus in the Netherlands, Biology alumnus Bart van Zijll Langhout…

Myrra Carstens

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.

The infectious diseases malaria and tuberculosis are responsible for 2.1 million deaths every year. Leiden researchers are currently testing a new tuberculosis vaccine.

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…

Seasonal influenza vaccines provide protection against matching influenza A virus (IAV) strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza…

Atherosclerosis (thickening of the artery wall) is the most common cause of heart attacks or strokes, and one of the most common causes of death in the western world. People with this condition have to take medicine all their lives, so a vaccine for atherosclerosis would be a breakthrough.

The Janssen-Cilag International N.V COVID-19 vaccine has received authorization for emergency use by the European Medicines Agency (EMA) on March 11. The vaccine was developed with fundamental support from the Molecular Virology group of the Leiden University Medical Centre (LUMC).

PURPOSE: The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination.

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

New and reemerging infectious diseases call for innovative and efficient control strategies of which fast vaccine design and development represent an important element.

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…

The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail.

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…

Tuberculosis is an infectious disease which is spreaded through the air. It is caused by Mycobacterium tuberculosis and it led 1.7 million people to death in 2016. This mortarlity rate is concentrated in developing countries such as Indonesia, Philippines, Pakistan, and South Africa. These numbers make…