Project Overview (live on website)

Drug delivery using nanomaterials has revolutionized medicine by improving efficiency and reducing side effects, creating a new branch, nanomedicine. Among nanomaterials, vesicles, self-assembled from phospholipids (liposomes) or block copolymers (polymersomes), provide mimics of biological membranes and allow delivery of drugs, genes and vaccines. Yet, they present limitations, such as poor mechanical properties or polydispersion. Recently, a simple method for the assembly of amphiphilic Janus dendrimers to produce monodisperse, stable and impermeable vesicles (dendrimersomes) with predictable dimensions and properties was reported. These dendrimersomes offer unexploited avenues for vaccinology as well as other areas of nanomedicine.

In vaccinology, a key to the development of a protective immune response is the ability to efficiently deliver the vaccine to antigen-presenting cells (APCs) and to induce their activation. APCs express sugar-binding C-type lectin receptors (CLRs) that mediate intracellular sorting of ligands, making them useful for antigen targeting. Recently, our team (R. Roy) reported the synthesis of Janus dendrimers with mannose and galactose in their hydrophilic part. These unprecedented sugarcontaining dendrimers are named Janus glycodendrimers and the obtained vesicles denoted as glycodendrimersomes (glyco-DM). Due to their multivalent scaffolds, glyco-DM possesses intrinsic adjuvant properties for antigen delivery by targeting CLRs and providing immunostimulatory activity for APCs. These novel APC-tailored nanocarriers, if properly designed, may thus improve antigen immunogenicity, and also open the door to other applications, such as cancer treatment and gene transfection.

Our hypothesis is that glyco-DM represent a novel platform nanotechnology to improve vaccine efficacy. The general aim is to understand the immunological basis and evaluate the potential of glycoDM as a novel antigen delivery system. Specific aims are:

1. Proof of concept: To evaluate the capacity of glyco-DM to enhance primary and memory antibody responses to the antigen.

2. Knowledge generation: To evaluate the capacity of glyco-DM to deliver antigens to APCs and further provide intrinsic adjuvant properties for immune cell activation.

Our team (Segura/Roy/Gottschalk) have been working during the last years in vaccine development against an important swine pathogen and emerging zoonotic agent: Streptococcus suis, which represents an ideal candidate to be used as a model. The economic losses caused by S. suis disease to the swine industry are very important and no efficacious vaccine is available. Two antigen candidates (a protein and a polysaccharide) are under experimental trials in our laboratories but their protective efficacy must be improved. These candidates will be used to evaluate the glyco-DM technology.

This project has two major contributions:

- Demonstrate that this tailor-made delivery system can induce improved immune responses against a antigen; thus providing the basis for a novel platform nanotechnology.

- Simultaneously, to develop an effective S. suis vaccine for veterinary use to reduce disease in swine; and, consequently, transmission to humans. Besides, it represents a prerequisite for a future vaccine in humans, especially for Asia, where S. suis has become a major problem.

→ The long-term goal is to translate the newly generated knowledge into future development of glyco-DM as tailored-delivery system not only for vaccinology but also for nanomedicine in general.