Grant: Operating Grant: Industry-partnered Collaborative Research

Nanoparticle vaccines can be highly effective but are generally quite expensive to make. A small biothecnology company in Quebec City (Medicago Inc) has found a way to make tiny virus-like particles (VLP) inexpensively in plants. When one or more viral proteins are placed on the surface of these VLP, they can act as powerful vaccines. Since there is no viral genetic information in the VLPs, these candidate vaccines are also very safe. We have developed animal models (mouse and ferret) and have performed 3 clinical trials of candidate VLP vaccines bearing either the H5 hemagglutinin of the highly dangerous avian flu virus or the H1 protein of the recent pandemic flu (a forth human trial is on-going). Results from both animal models and human trials suggest that these vaccines are unusually effective at stimulating strong immune responses. Preliminary data suggests that these vaccines work well administered by needle in either the muscle or the skin (animals. human) or inhaled into the nose (animals). For several years now, we have been working with Medicago to better understand how these plant-made vaccines work. So far, we have shown that the VLP vaccines interact rapidly with both animal and human immune cells to promote both immediate (innate) and long-lived (adaptive) immunity. We propose to continue these studies in more depth to fully understand what elements within the VLP drive this effect. We have also succeeded in making VLP vaccines with influenza HA protein on the surface and a fluorescent molecule (eGFP) on the inside. We have just begun to use these unique reagents to study how the VLP vaccines interact with individual immune cells and how they move within the immune system. The studies we propose are critical to understanding how these extraordinarily promising vaccine candidates actually work.