Vaccination via the skin or the mucosae

Leiden researchers are helping develop safe COVID-19 vaccines.

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

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

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

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

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…

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

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…

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.

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.

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

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.

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

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

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.

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.

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

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.

Promotores: Wim Jiskoot; Ferry Ossendorp

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.

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

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.

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.

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

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.

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…

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

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 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.

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

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

Promotores: W. Jiskoot, F. Ossendorp

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.

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.

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.

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.

The potential of bioneedles to deliver influenza vaccines was investigated.

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…

The potential of liposomal cancer vaccines

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.

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.

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.

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…

Dr. Gideon Kersten is professor of Vaccine Delivery at the Division of BioTherapeutics.