Title Affiliations Abstract "Evaluation of the potential of Boldoa saponins as vaccine adjuvants" "Natural Products and Food - Research and Analysis (NatuRA)" "Vaccines are one of the most effective health interventions ever developed and remain as one of the best shots to prevent epidemic diseases. Generally, traditional vaccines (live, but attenuated, or inactivated whole organisms) and new generation vaccines (e.g. recombinant proteins, purified antigen and DNA) are poorly immunogenic due to lack of effective immune stimulus. Therefore, adjuvants in vaccine formulations have become increasingly important ingredients to increase the immunological efficiency and improve vaccination schedules. Currently, over 100 potent adjuvants have been reported. However, most of them cannot be licensed for human use because of their undesired side effects. Even the most common chemical adjuvant(s) approved for use in licensed human vaccines (e.g. Alum; FDA approved, but neurotoxic) produce unwanted side effects including pain at injection site, inflammation, lymphadenopathy, granulomas and sterile abscess, among others. Due to toxicity issues, there is a critical need to develop or identify adjuvant molecules that initiate a potent immune response with less reactogenicity and less systemic toxicity. In this study, we propose to identify and investigate benchmarking candidate adjuvants based on saponins from Boldoa purpurascens which are safe and less toxic (preliminary results) than other adjuvant saponins (QS 21). The discovery of new saponin-adjuvant from this study would lead to more efficient vaccines aiming to elicit a specific, protective and long-lasting immunity after vaccination. The central research hypothesis of this study is that new saponins purified from Boldoa leaves and stems would exert the immune adjuvant activity without exhibiting systemic toxicity. To study this hypothesis, we will isolate the saponins and fully characterize their chemical structure. Their haemolytic and cytotoxic activity will be determined and the most promising saponin(s) and/or well characterised saponin fraction(s) will be evaluated in vitro on their potential as vaccin adjuvant." "The potential of Lactobacillus exopolysaccharides and glycoproteins as safe vaccine adjuvants." "Sarah Lebeer" "Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Environmental Ecology & Applied Microbiology (ENdEMIC)" "Ligands of the innate immune system form an important new class of adjuvants, but the desired immunostimulation is often linked with toxicity and serious side-effects. These ligands or 'microbe-associated molecular patterns' (MAMPs) can also be found on the surface of lactobacilli with a 'generally regarded as safe' status. Various studies have demonstrated the specific effects of certain lactobacilli and their surface molecules, but the potential of MAMPs such as exopolysaccharides and glycoproteins of lactobacilli still requires further investigation. Hereto, the project is divided in three parts. First, the molecular interactions between the glycoconjugates and receptors such as Toll-like receptors and C-type lectins will be mapped. Next the in vitro immune response of these molecules in immunological important cells will be investigated. Finally, the potential of selected molecules will be validated in a mouse model." "LNP-DECODE: Deciphering the adjuvants activity of lipid nanoparticle-based mRNA vaccines in primary dendritic cells" "Stefaan De Smedt, Jonathan Maelfait, Sophie Janssens" "Department of Pharmaceutics, Department of Biomedical molecular biology, Department of Internal Medicine and Pediatrics" "This project aims to put UGent at the forefront of mRNA-vaccine research by providing in-depth insights in the adjuvant properties of LNP-based mRNA-vaccines. To this end, we will join the expertise of 3 teams working on dendritic cell biology, nucleic acid sensors and lipid nanoparticles respectively.This consortium will form the basis for the development of vaccines against autoimmune diseases." "The working mechanism of a new class of adjuvant, the Layered Double Hydroxide (LDH) family." "Department of Internal medicine" "This interdisciplinary project combines key aspects of chemistry and immunology to predict which members of a new class of adjuvants, the Layered double hydroxide family (LDH), induce a better cellular and/or humoral immune response than the common used adjuvant alum. Besides, we will unravel their cellular and molecular mechanism of action and their applicability in an influenza infection model." "A novel, DNA-based, live-attenuated vaccine for the yellow fever virus and other medically important flaviviruses." "Johan Neyts" "Laboratory of Virology and Chemotherapy (Rega Institute)" "Many vaccines are still composed of a purified antigen or a whole, inactivated pathogen combined with adjuvants. Alternatively, as is the case for yellow fever virus (YFV), measles, mumps and rubella, purified, live-attenuated virus vaccines are available. Both types of vaccines are expensive to produce and require a cold distribution chain from manufacturer to patient, which is in particular hard to achieve in resource-poor or remote settings. Therefore, DNA vaccines are projected to be the future in vaccination. We recently developed a novel, robust and convenient reverse genetics system that, after administration as a DNA vaccine, launches with high efficacy the same live-attenuated virus that is present in the current YFV vaccine. This DNA vaccine would no longer require the production of the live-attenuated virus in fertilized chicken eggs, which would make it much cheaper and easier to produce, store and distribute. This approach should also be applicable for the development of vaccines against flaviviruses related to YFV (such as the Japanese encephalitis and West Nile virus), as well as other viral pathogens." "Dendritic cells as a potential target for the development of an atherosclerosis vaccine." "Dorien Schrijvers" "Vaccine & Infectious Disease Institute (VAXINFECTIO), Physiopharmacology (PHYSPHAR)" "Acute cardiovascular syndromes (e.g. myocardial infarction and stroke) are a major cause of morbidity and mortality in industrialized countries. They result from rupture and subsequent thrombosis of an atherosclerotic plaque that has built up in the wall of large and middle-sized arteries. Chronic inflammation, mediated by dendritic cells (DCs) drives the development of atherosclerosis. DCs are present in healthy arteries in areas predisposed to atherosclerotic plaque formation, and accumulate within plaques where they can be localized in close vicinity to T cells. Recent work has revealed important functions of DCs in regulating inflammatory and immune mechanisms in atherogenesis. In addition to antigen presentation to T-cells with subsequent activation, DCs themselves will secrete inflammatory cytokines (e.g. IL-12), further exacerbating atherosclerosis. Because of their unique properties (capable of inducing either immune responses or immune tolerance), DCs can be harnessed to suppress unwanted responses, in the form of vaccines. Vaccination strategies using DCs are currently being explored in various diseases. In fact, the approval of Provenge® (the first ""DC vaccine"" for prostate cancer) by the FDA in 2010 has paved the way for further development of DC vaccines. Our central hypothesis is that a vaccine-based approach to manage atherosclerotic cardiovascular disease is a potentially viable strategy. In fact, the first proof of concept that this approach could be very useful in combatting cardiovascular disease came very recently from the group of Goran Hansson. Treatment of mice with in vitro generated tolerogenic DCs attenuated atherosclerotic plaque development. However, these DCs have an unstable phenotype. Therefore, in this project we aim to (1) identify biomarkers for plaque DCs for targeted immunotherapy, (2) generate stable, tolerogenic DCs using RNA interference to suppress autologous T-cell activation and (3) study the effects of siRNA mediated DC targeted IL-12 silencing on atherosclerotic plaque progression and stability in mice.This research program is part of a global research effort to develop new therapeutic approaches for atherosclerotic plaque stabilization. Specifically, the current program aims to elucidate whether or not modulation of immune responses can stabilize atherosclerotic plaques." "Polymer-lipid amphiphile carriers for small molecule immune-modulators" "Bruno De Geest" "Department of Biochemistry and microbiology, Department of Pharmaceutics" "The aim of this Concept TT is to obtain a technical proof of concept that shows the potential of polymer-lipid amphiphiles as carrier for lymph node-targeted delivery of small molecule immuno-modulators. Ultimately, the research results will be used to support a patent application." "Adjuvanting aminopeptidase N-targeted oral vaccines to protect against gut pathogens" "Bert Devriendt" "Department of Translational Physiology, Infectiology and Public Health" "Aminopeptidase N-mediated delivery of vaccine antigens to the gut immune system holds great promise to develop efficacious oral vaccines to combat gut pathogens in pigs. This project builds further on previous data showing protective immunity against infection with pathogenic E. coli induced by oral vaccination of piglets with aminopeptidase N-targeted vaccine antigens. In this project, we aim to optimize the design of our aminopeptidase N-targeted vaccine candidate to increase its manufacturability as well as to improve its immunogenicity. The latter will allow to obtain a sufficient efficacy to protect pigs against pathogenic E. coli infection in field conditions. The generated data will be used to increase the valorisation potential of our aminopeptidase N gut delivery platform." "Synthetic mycolic acids for therapy of asthma and as adjuvants for vaccination" "Johan Grooten" "Department of Biomedical molecular biology" "geen abstract" "ESCAPE - Enhanced nanoformulation based on layer-by-layer polyelectrolyte submicroparticles conjugated with cationic peptides" "Joeri Aerts" "Internal medicine, Clinical sciences, Pharmaceutical and Pharmacological Sciences, Neuro-Aging & Viro-Immunotherapy" "Although mRNA has been explored as a gene delivery strategy for several decades, and several companies have been established around the mRNA vaccine development, its use as a vaccination platform only burgeoned in the past few years thanks to the tremendous success of the COVID-19 vaccines. This success can be attributed to several factors including a longstanding experience with mRNA manufacturing and clinical use in various settings, the availability of suitable carriers under the form of lipid nanoparticles (LNPs) and a relatively stable viral genome in SARS-CoV-2 compared to other viruses such as influenza and HIV. However, although mRNA-based vaccines Template application PoC-projects – 2nd call 2023 have clearly proven their potential in the COVID-19 pandemic, this does not mean that it represents a one-size-fits-all solution for all kinds of diseases. Although we have probably learned more about mRNA-based vaccines during the last three years than during the three decades before, it is clear that other, more complex diseases such as HIV and cancer, require more elaborate approaches for mRNA to be successful in the treatment of these diseases. Next to the judicial choice of the targets encoded by the mRNA, one of the most important issues is the context of delivery of the mRNA, which in large part is determined by the nanoparticles in which it is formulated. Although LNPs have proven to be a suitable mRNA delivery system in the context of COVID-19, they also have clear limitations, including storage and handling requirements with an important cold chain, requiring ultralow temperatures for long-term storage, the lack of functionalization, as the fluid aspect of LNPs severely limits the type of molecules that can be incorporated, a relatively high cost, limited amount and size of mRNA to be formulated, and uncontrolled immune responses. Based on a longstanding expertise with the development of mRNA based therapeutic vaccines against HIV, our laboratory has evaluated several candidate nanoparticles that could potentially overcome some of the issues related to LNPs. Thus, by combining cationic peptides, a formulation which we previously established in the lab as an excellent carrier for mRNA, with the so-called layer-by-layer (LbL) approach, where layers of cationic and anionic moieties are interchangeably deposited on a calcium carbonate core, like the layers of an onion, we showed that this formulation has many advantages over LNPs: it is cheap and easy to produce, and has potential for upscaling, it is very stable, even at room temperature, thus potentially overcoming important cold chain issues, it efficiently transfects many different cell lines, including dendritic cells, with different kinds of mRNA, including self-amplifying RNA which is very large and difficult to formulate. Finally, a very important asset is the flexibility in functionalizing these nanoparticles, as various organic or inorganic molecules can be incorporated in the core, between the layers or on the outer layer. These include targeting signals, adjuvants, small molecule drugs, fluorophores for in vivo imaging, and even light or magnetic field triggered release of cargo. In this PoC project, we want to further improve our formulation by systematically permutating the different components (core, layers and outer layer) with the aim to develop a flexible mRNA vaccine delivery platform, that can be used for various indications, not only in a prophylactic setting but also as a therapeutic vaccine in difficult to treat diseases such as cancer and HIV infection. In this way we want to strengthen our intellectual property position and bring our formulation closer to the market and to the clinic."