Vaccine Stabilizing Silica-Coating Technology

Technology Overview

Portland State’s technology uses silica as a nano-scale encapsulation agent for vaccine (viral vectors, LNPs, proteins, etc.) stabilization. The silica treatment not only causes enhanced cellular uptake, but also increases thermal stability. As a proof of concept, researchers have observed significantly enhanced gene transduction into cells with silica-treated adenovirus ( A compared to 1B). In addition, silica treatment stabilizes adenovirus to inactivation due to multiple freeze-thaw cycles (Figure 1C compared to 1D). Flow cytometry data with Vero cells and RAW 264.7 cells demonstrate that silica treatment leads to at least 10 fold more cells being transfected and much higher amounts of GFP fluorescence ().

Silica-treated Vaccina virus (VACV) and live attenuated influenza virus (LAIV) both induce robust cellular immune responses when injected (VACV) or introduced intra-nasally (LAIV) in mice with no observed ill effects (Figure 2) suggesting the versatility of silica treatment in a functional model.

Together with the previously published data on silica-treated viruses being exceptionally resistant to drying, researchers found that silica-treatment of vaccines can stabilize them to multiple freeze-thaw cycles (Figure 1) and are highly likely to generate robust and protective immune responses ().

In addition to Adenovirus, researchers have shown enhanced virus cellular uptake with silica-treated Mouse Cytomegalovirus (unpublished). They have also shown that yellow fever virus vaccine strains and small ssDNA viruses similar to adeno-associated virus can be reversibly coated in silica (unpublished) indicating that many virus types can be coated with silica.

No cellular toxicity of the silica-treatment was observed in the Vero cells and the silica-treatment does not cause hemolysis (data not shown). Also, no adverse effects were observed in mice injected with silica-treated adenovirus, or inoculated intra-nasally. Silica nanoparticles made in a similar manner to the silica-treated virus particles here have been used in clinical studies and silica itself is classified by the FDA as “Generally Regarded as Safe” for ingestion.

Silica-treated adenoviruses “cloaks” adenovirus vectors such that there is a markedly lower adenovirus-specific antibody response in mice with silica-treated adenovirus relative to untreated adenovirus. Enhanced gene delivery by silica-treated adenovirus into multiple different cell lines was also demonstrated as well as much lower liver targeting of silica-treated adenovirus compared to untreated virus.

Others have shown that silica-treatment of poliovirus vaccine and enterovirus 71 stabilize both to prolonged exposure to temperatures up to 42C while still maintaining the ability to generate antibodies. The Protein-based vaccine tetanus toxoid C-fragment can be stabilized to treatments at 80C without losing antigenicity by silica-treatment. Finally, a silica-treatment and freezing can be used to generate tumor cells with enhanced immunogenicity, ability to enter immune cells, and stability that could be useful as cancer vaccines.

Opportunity

With this exciting preliminary data, strong IP position, and proof of concept work Portland State is actively seeking collaborations to advance this technology towards the clinic.
Portland State University has patented technology and is looking for partners for joint vaccine development.