TLR2 are present on the surface of dendritic cells and binding of the TLR2 by TLR2 agonist results in dendritic cells maturation through activation of the MyD88 signalling pathway. Because TLR2 is an endocytic receptor, any antigen complexed to a TLR2 agonist will be transported into the dendritic cells where it is processed and presented in the context of class I and II molecules of the major histocompatibility complex (MHC). The antigen-loaded and matured dendritic cells are then capable of activating naive antigen-specific CD8+ and CD4+ T cells and of eliciting strong T and B cell immune responses.
lnnavac’s TLR2 agonists, have been engineered to incorporate a unique charged, branched structure capable of complexing (through electrostatic interactions) recombinant protein antigens, without any chemical intervention or modification. This simple plug and play system which does not need any modification of recombinant antigens, facilitates the delivery and processing of protein/peptide-based antigen cargo to TLR2 expressing antigen presenting cells, such as dendritic cells.
Using the split influenza virus vaccine model, lnnavac founders led by Professor David Jackson, have shown that Innavac’s TLR2 agonists can be formulated with multiple different antigens to elicit both neutralizing antibodies against the homologous influenza virus as well as CD8+ T cell responses that can protect against virus of a different subtype. Formulation of lnnavac’s TLR2 agonists with an otherwise ineffective dose of the 2013 trivalent seasonal vaccine results in an approximately a one-thousand fold increase in antigen-specific antibody titre compared to the use of vaccine alone. These results demonstrate that this adjuvant allows a dose-sparing vaccination regime.
- Chua et al. 2011. Soluble Proteins Induce Strong CD8+ T Cell and Antibody Responses through Electrostatic Association with Simple Cationic or Anionic Lipopeptides That Target TLR2. J Immunol. 2011;187;1692-1701
- Chua et al. 2014. The use of a TLR2 agonist-based adjuvant for enhancing effector and memory CD8 T-cell responses. Immunology and Cell Biology (2014), 1–7.
- Chua et al. 2015. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity. mBio.2015; 6; e01024-15
Key advantages of Innavac's TLR2 agonists:
- Easy way to “adjuvant” protein recombinant-based vaccine cargo (plug & play)
- Ability to complex and deliver recombinant protein antigen to DCs leading to the induction of strong T-cell mediated & antibody responses
- Simple, robust and low cost of manufacture (synthetic molecule)
- Mucosal immune responses
- Defined mechanism of action
- Patented technology