Associate Professor, Biodesign Center for Immunotherapy, Vaccines and Virotherapy
Hugh Mason was the first to publish peer-reviewed work on the use of plants for production of vaccine antigens, showing expression of authentic hepatitis B surface antigen in tobacco (Mason et al., 1992). He has been a leader in this field for many years and continues to publish work in plant-based vaccines (Kim et al., 2015). With funding from NIH-NIAID, his lab focused on oral delivery of vaccines for enteric diseases including Norwalk virus (Mason et al., 1996) and enterotoxic E. coli (Haq et al., 1995), and demonstrated oral immunogenicity in mice after ingestion of transgenic potato tuber. These studies were seminal to a field that is now strongly developed worldwide. His group's work on expression of vaccine antigens in potato led to the first human testing of plant-based vaccines, funded by NIH-NIAID. The first such trial ever conducted showed that volunteers who ate potato tuber expressing E. coliheat-labile enterotoxin B subunit (LTB) developed serum and mucosal antibodies specific for LT-B (Tacket et al., 1998). The next study demonstrated specific antibody responses in humans who ingested potatoes expressing Norwalk virus capsid protein (NVCP) (Tacket et al., 2000). A third trial showed substantial boosting of titers of serum antibodies against hepatitis B surface antigen (HBsAg) in people who were previously vaccinated with the commercial yeast-derived HBsAg vaccine (Thanavala et al., 2005). Although only a few other clinical studies have been published on plant-based vaccines, his lab's work demonstrated the potential for the strategy and spurred other research leading to plant-based veterinary vaccines (Mason et al., 2013).
With funding from DARPA, Professor Mason and coworkers developed a rapid and robust plant-based expression system using a geminivirus, bean yellow dwarf virus (Mor et al., 2003). Later, funded by NIH-NIAID, the group showed that it could produce Norwalk virus VLP at ~0.5 g per kg leaf mass (Huang et al. 2009). Moreover, it was enormously useful for co-expression of multiple different proteins, and thus allowed production of anti-Ebola monoclonal antibody at high levels (Huang et al., 2010). This work resulted in a patent for use of geminiviral vectors for rapid transient expression in plants. His latest work shows further enhancement of expression using vector refinements and ancillary elements incorporated into the geminiviral replicons (Diamos et al., 2016).
With funding fro NIH, the Mason lab used the geminiviral transient plant expression system to produce a RIC vaccine for Ebola virus (Phoolcharoen et al., 2011a). This novel approach enables production of immune complexes by expressing a self-reactive antibody via fusion of the target antigen to the C-terminus of the heavy chain and co-expression of the light chain. The Ebola RIC used the viral glycoprotein GP1 and provided protection to mice against lethal virus challenge (Phoolcharoen et al., 2011b). We further developed this system to make a universal RIC platform, by tagging vaccine antigens with the Ebola GP1 epitope. This resulted in a robust anti-dengue vaccine that produced neutralizing antibodies after only two vaccinations without adjuvant (Kim et al., 2015). These results show strong potential for RIC produced in plants with geminiviral vectors.