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Our dendritic polyglycerol-based nano-adjuvants, are tailor-made nanodrug formulations with extremely narrow and controlled size distribution anywhere between 8 and 120 nm. Thus, systems in the ideal range of 30-50 nm for transport into the lymphatic system are feasible. Both lipophilic and hydrophilic co-adjuvants can be transported. Due to the excellent match between the core-shell interaction of the aliphatic partition of its amphiphilic double shell the system is also well suited for the uptake, transport and release of novel Th1 and Th2 enhancers like octocosanol, squalane, and tocotrienol, which are subject to our current developments.
Further selective targeting can be achieved by functionalizing the core and shell molecules. This results in a tailormade charge distribution that can be adapted specifically towards the needs of specific protein and nucleic acid-based drugs
A NEXT-GENERATION BIOPOLYMER
In order to induce a lasting immune response, vaccines need to reach the lymphatic system and in particular the lymph nodes. In order to reach these targets, a fine dispersion of the antigen is mandatory to prevent uptake by macrophages which would compromise the immune response. Thus, optimizing the transport pathways of vaccines are a salient part of adjuvant action and efficacy.
Our dendritic nano-adjuvants stabilize the antigens in the final formulation, therefore preventing clumping and enabling a fast reconstitution. Furthermore, stabilization of the vaccine after injection in dermal and intradermal tissue is obtained to further achieve a disperse formulation that can be readily taken up by dendritic cells. Our carriers have a proven ability to enhance the uptake of particles and assisting the penetration of co-adjuvants into dendritic cells, facilitating a rapid transport towards the lymph nodes.
Further selective targeting can also be achieved by functionalizing the core and shell molecules. This results in a tailormade charge distribution that can be adapted specifically towards the needs of specific protein and nucleic acid-based drugs.
The technology uses compounds which have been tested for preclinical safety and which are manufactured according to good manufacturing practice.
MECHANISM OF ACTION
AN INNATELY ATTRACTIVE ADJUVANT
Our dendritic nano-adjuvant formulations are designed to enhance the immune response to vaccine antigens both quantitatively (higher levels) and qualitatively, with differences in the profile of the elicited antibody response. After intramuscular inoculation, it stimulates an influx of inflammatory cells, including granulocytes as well as monocytes and macrophages to the injection site.
Their release of chemokines, including CCL2, 3, 4, and IL18, attract further waves of inflammatory cells, establishing a localized immunostimulatory environment. Co-administered antigen at the site is actively taken up by monocytes while the dendritic nano-adjuvant also induces the chemokine receptor CCR7 and, given its size (approximately 50nm), allow for a disperse uptake and increase of differentiation into dendritic cells and its migration into draining lymph nodes where it triggers the adaptive immune response specific to the vaccine antigen.
The resulting proliferation of antigen presenting cells and helper T cells then augment a B cell response and ultimately, increased production of antibodies.
The individual components of our dendritic nano-adjuvant formulations, including the novel squalane (the hydrogenated stable form of unstable squalene), are not in themselves adjuvants. An adjuvant effect is seen only with the microfluidized formulation comprising all components. The antigen and the dendritic nano-adjuvant must be presented at the same site for an adjuvant effect to be seen and presented either at the same time or with the dendritic nano-adjuvant presented first, allowing the adjuvant to establish the immunostimulatory environment of immune-reactive cells that leads to increased uptake and processing of antigen.