Heather Callaway, Ph.D.

What if we could design longer-lasting vaccines?

Rabies virus is the source of an ongoing global pandemic that affects both humans and animals. Untreated rabies infection is nearly 100% lethal, and in spite of the existence of rabies vaccines, rabies continues to kill over 50,000 people every year and places a significant financial burden on the livestock industry. One reason rabies persists is because vaccine protection is short-lived. After about a year, anti-rabies antibodies decline and are no longer protective, necessitating annual repeat vaccinations to maintain immunity. Post-exposure treatment for rabies is also possible, but consists of multiple doses of rabies vaccine and expensive antiviral antibodies, making it unaffordable in low-income countries where most rabies deaths occur. To prevent these deaths, we need an effective, long-lasting rabies vaccine so that vulnerable individuals only need to be vaccinated once.

Rabies vaccines work by generating antibodies against the rabies glycoprotein, the only protein on the surface of rabies virus. In order to develop a robust, long-lasting immune response, a vaccine needs to present multiple copies of identically shaped rabies glycoprotein trimers (three glycoproteins forming a functional unit) to the immune system. However, rabies glycoprotein is unusually heterogeneous and adopts multiple shapes, making it difficult for the immune system to ‘see’ the right forms of rabies glycoprotein to generate long-lasting antibody producing cells. In the Saphire lab, I have engineered a stabilized version of the rabies glycoprotein to greatly reduce its heterogeneity. With SPARK award funding, I plan to vaccinate mice with this newly stabilized protein and test how the immune system responds to stabilized rabies glycoprotein compared to existing vaccines containing heterogenous, unmodified rabies glycoprotein. I will determine if the immune response is longer lasting after vaccination with stabilized glycoprotein and isolate anti-rabies antibodies that can be used both to develop more potent antiviral therapies and to further engineer the rabies glycoprotein to improve vaccines. If successful, I will obtain preliminary data that will give valuable insight into the production of an improved, long-lasting rabies vaccine and potent antiviral antibodies, and allow me to apply for additional funding for larger scale testing.

SPARKing Impact: This study lays the groundwork for the design of an effective and most importantly, longer-lasting rabies vaccine, which would help save tens of thousands of lives every year.