About CD40 Ligand (CD40L)
CD40L is a trimeric molecule in the TNF SuperFamily. It has been produced in a soluble trimeric form yet this form does not sufficiently activate cells bearing the CD40 receptor. Instead, activation of CD40-positive cells requires many trimers in order to cluster the CD40 receptors in the membrane of the responding cell. In the case of dendritic cells (DCs), CD40L activates these cells to present antigen to CD8+ T cells which then divide and move throughout the body.
FortiVac™ Molecular Design
Genetic engineering is used to fuse the CD40L extracellular domain with the body of surfactant protein D (SPD) – a natural protein that spontaneously self-assembles into a 12-chain protein. This results in a nanostructured protein with four trimeric CD40L domains at the end of each collagen-like “arm” of SPD. This is a remarkably stable protein (active at room temperature for >1 week) that stimulates DCs in a manner similar to natural membrane CD40L. In addition, the molecule contains amino acid sequences for the antigen of interest. The resulting fusion protein allows DCs to take up the antigen via their CD40 receptor, which is an ideal way to load these cells with the antigen target.
Vaccines for CD8+ T cells
There is a significant unmet need for vaccines that generate high levels of CD8+ T cells. Once produced, CD8+ T cells are capable of eradicating tumors, preventing or treating viral infections (chronic hepatitis B virus infection, influenza, ebola, dengue, and other viruses), and providing protection from malaria. The missing step is a vaccine technology that stimulates the body to make these much needed CD8+ T cells. FortiVac fulfills this need.