Designing novel particulate vaccination strategies to evoke cytotoxic T cell responses against chronic intracellular infections

01 January 2014 → 31 August 2016
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Other biological sciences
particles vaccination pathogen
Project description

To combat insidious pathogens such as HIV, malaria, HCV and tuberculosis, there is an urgent need for new vaccination strategies that can effectiveley evoke cytotoxic T cells, which have the unique potential to recognize and kill infected cells. In this project, two conceptually different approaches are envisioned to achieve this goal. Both strategies require nano/micro formulation, a key expertise within the lab.
The first appraoch is based on the encapsulation of protein antigens and immunomodulators in micron-sized particles that mimic the dimensions of bacteria and are therefore perceived by the immune system as dangerous. Earlier, we have developed an easy to scal eup single step process based on spray drying to produce such particles. Here, we further aim to optimize this process in order to obtain particles more ideally suited for cytotoxic T cell induction.
The second appraoch is based on the use of antigen encoding mRNA instead of protein based vaccines. Previously, we have demonstrated that delivering the antigen encoding mRNA as lipoplexes allows the induction of cytotoxic T cells. The mRNA lipoplexes however also induced the expression of type I IFN, evoking an antiviral status upon the cells that interfered with the translation of the mRNA and the subsequent induction of the immune response. In the second part of this project, we aim to modulate this antiviral response to maximize antigen expression and cytotoxic T cell induction.