Almost all viruses, including Coronavirus, Influenza and Respiratory Syncytial Virus (RSV), gain entry by binding to receptors present on luminal mucosal epithelial cell surfaces. Once they have crossed the mucosae, the virus must find, bind and enter suitable host cells to replicate. To counter the influx of pathogens, mammals have developed an innate mucosal immune system as a first line of defense, blocking or destroying foreign particles right at the port of entry.
Systemic immunity kicks in as a second line of defense after viral replication has started. Infected cells will present viral peptide fragments on their surface through MHC signaling. These foreign peptides will be recognized by T-cells, initiating a series of events that result in the production of antibodies.
Today, most vaccines are being administered by intramuscular injection, activating the systemic immune system but not the mucosal immune system. While these vaccines are effective at preventing severe diseases and death, they do little to actually prevent viral infection and spread.
Transmucosis has developed a mucosal vaccination platform that is able to induce both mucosal and systemic immunity. We’ve successfully demonstrated this dual mode of immune activation both in mice and hamsters. We are now preparing for human clinical trials.
Our platform is differentiated by how it leverages the unique properties of the FcRn receptor. For context, the FcRn receptor is abundantly expressed on epithelial cells and binds under mild acidic conditions to the Fc region of IgG. Its physiological role is to extend IgG half-life and transport IgG antibodies across epithelial cell barriers. Transmucosis is exploiting these unique properties of the FcRn receptor by making DNA constructs coding for viral antigens linked to Fc, thus mimicking heavy chain IgG antibody molecules.
Upon nasal delivery, our vaccine molecules bind to Fc receptors in the nasal cavity and are transported across the epithelial cell barrier into the mucosal tissues where they elicit a secretory IgA and tissue-resident memory Tcell response. Our vaccine molecules also enter the circulation, transported by FcRn receptors present on endothelial cells lining the microvasculature, where they elicit a systemic Tcell and IgG response.