KGI Team Adapts Vaccine Development Work to Address COVID-19

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A research team at the Keck Graduate Institute will work to adapt its decade-long low-cost vaccine R&D for developing countries into a COVID-19 vaccine.

On Aug. 11, 2021, the Keck Graduate Institute (KGI), based in Claremont, Calif., announced that its dean of research and research professor, Larry Grill, and his team will work on adapting the low-cost vaccines on which they have been working on for the past decade for use against COVID-19.

Grill and his team have been working for the past 11 years to produce low-cost vaccines for developing countries. They have been primarily focused on animal diseases that significantly impact smallholder farmers in Africa but had not considered developing vaccines for the US market because of the length of time typically needed to get vaccines approved by FDA. Grill has shifted focus based on the current emergency use authorization brought on by the pandemic. He and his team are now working to adapt a vaccine candidate they have been working on for use against COVID-19. Grill’s vaccine is derived from plant viruses, making it distinct from the COVID vaccines currently on the market, according to a KGI press release.

Plant viruses are not known to cause diseases in humans but can still induce an immune response. Viruses from plants can therefore be used to train the immune system to respond appropriately to antigens by disguising the plant virus with a surface protein that mimics the target pathogen.

Grill and his team are taking advantage of this feature by changing the outside surface of the plant virus to resemble a real pathogen. To make the adaptation, they used a virus coat protein fusion to add the genetic information from a SARS-CoV-2 spike protein to the surface of a tobacco mosaic virus (TMV). The TMV fused coat proteins are taken up by antigen presenting cells (APCs) and displayed on class II major histocompatibility complex molecules (MHCs). The class II MHCs interact with CD4+ T cells to trigger an appropriate cellular immune response.

“Your immune system detects the virus and makes antibodies against the SARS-CoV-2 spike protein,” Grill said in the press release. “As a matter of fact, the data that we have shows that memory cells would be ready for the SARS-CoV-2 virus for at least a few years.”

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Manufacturing logistics

The team can grow the TMV vaccines in plants, allowing for large production volumes of what Grill calls “decorated viruses”. They are working with Botswana Vaccine Institute and the Botswana government to secure funding to build a facility in Botswana to produce the vaccines at low cost for developing countries.

The plants used for vaccine production are grown in growth rooms and leaves are harvested eight to 10 days post introduction. From there, the TMV vaccines are purified with a simple precipitation step. Produced this way, the virus for the vaccine is stable and doesn’t necessarily need to be stored at extremely cold temperatures. Cold-temperature storage would be problematic when transporting the vaccine to developing countries, according to Grill in the press release.

Source: Keck Graduate Institute