Development of a new platform of vectorization of biologically active molecules: application to antigen/adjuvant delivery to dendritic cells for vaccination – OPTIVAC

Vectorization of biologically active molecules for their selective delivery to target cells is a major objective since this strategy allows potentiating the activity of these molecules, but also limiting their side effects. In particular, selective addressing of antigens of vaccinal interest to dendritic cells represents an active field of investigation and is particularly promising for the development of new candidate vaccines against infectious agents or cancers. Indeed, the dendritic cells are the only cells of the innate immune system able to activate the naive T cells, which is indispensable to induce protective adaptive immune responses. According to their phenotype, ontogeny, localization and specialized functions, dendritic cells are divided into different subpopulations, including lymphoid, myeloid and plasmacytoid subsets, identified both in mice and humans. A large body of data shows that the level of adaptive immune responses, differentiation and specialization of CD4+ Th1, Th2, Th17, or regulatory T cells, as well as activation of CD8+ T cells are orchestrated by various sub-populations of dendritic cells. Therefore, the in vivo mobilization and activation of the latter by their direct targeting through specific surface markers, represents a critical way for the development of preventative and/or therapeutic vaccine candidates against cancers or infectious diseases.
We have recently developed a vectorization technology to address one or more biologically active molecules, including antigens and/or adjuvants, in a highly versatile manner, to various target cells and in particular to dendritic cell sub-populations. Unlike other technologies developed to date, our strategy allows the addressing of biologically active peptidic or non-peptidic compounds to well-defined dendritic cell subsets. Indeed, these compounds can be polypeptides, sugars, lipids or oligonucleotides of large size. Application of this technology to vaccination will enable to deliver in a highly specific and well-controlled manner, necessary and sufficient amounts of antigens and adjuvants to the same sub-population of dendritic cells, selected as a function of the type of the adaptive immunity to be induced. This will allow inducing optimal and ultimately protective immune responses, without undesirable inflammatory responses, frequently related to administration of adjuvant.
We have established the proof-of-concept and feasibility of this approach in different experimental models, ranging from synthesis and purification of vectorized molecules until in vivo induction of adaptive immune responses. All of these results gave rise to a European patent application in December 2009. Our current project aims to reinforce the results obtained, in order to substantiate claims of the patent and strengthen intellectual property protecting the developed technology. Furthermore, the objective of our project is the implementation of our technology for the development of effective therapeutic and/or prophylactic vaccines in priority areas in public health and economic level, such as adult pulmonary tuberculosis and cancers due to chronic Human Papillomavirus (HPV) infection. The present proposal will lead to a rapid valorization of this technology at the industrial level.