Projects / Programmes
Development of innate immune receptor-targeting chimeras as custom-tailored vaccine adjuvants
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
adjuvants, vaccines, innate immune agonists, conjugates, formulation
Researchers (13)
Organisations (1)
Abstract
Currently, our world is facing an acute shortage of novel vaccine adjuvants. Adjuvants enhance the immunogenicity of vaccines, therefore they constitute essential components of vaccines. They are needed not only to increase the magnitude of the response but also to guide the type of response to produce the most effective type of immunity against distinct pathogens/tumors. The recent progress in our understanding of innate immunity has opened up new avenues for vaccine development. The innate immune system is comprised of APCs, in particular dendritic cells (DCs), which contain a series of pattern recognition receptors (PRRs). PRR agonists engage DCs to more effectively uptake and present antigens and provide indispensable initial signals that determine the type, magnitude and durability of adaptive response, therefore they constitute promising leads in vaccine adjuvant development. Simultaneous activation of distinct PRRs permits signal amplification. Covalent linkage of several PRR agonists can further enhance their adjuvant activity. Finding synergistic combinations of adjuvants to produce potent immune responses is therefore crucial for rational design and development of vaccines. Our critical research goal is to develop innovative adjuvants capable of enhancing the immunogenicity of different vaccines. In the scope of this project, we propose an advanced multi-targeted approach to adjuvant development, by imparting the synergies of innate immune system to a single molecule. To achieve this, we will use an advanced chemical strategy to direct the immune system by constructing covalently linked multivalent agonists with unprecedented synergistic combinations. These conjugates will allow for simultaneous targeting of multiple targets within the same cell, thus enabling cross-activation of several arms of the innate immune system. Since liposomes and nanoparticles have successfully been used as carriers of antigens and adjuvants and also promote a potent cellular response while improving compound stability against enzymatic stress, our conjugates will be formulated in these carriers. The ground-breaking results of this project will allow us to harness the full strength of immune system and pave the way for a next-generation vaccines. Beyond this, it can be foreseen that these highly innovative adjuvants will find medical applications as part of vaccines for treatment of infectious diseases thus improving public health, while our findings will also reveal fundamental new information about how immune cells operate and uncover the underlying mechanisms.
