mRNA-Based Vaccines Against Tick Borne Thogotoviruses

The incidence of tick-borne diseases has increased significantly over the past 25 years due to climate 1 change, shifting population demographics of both humans and ticks, and inadequate vector control. 2 Including economic and societal costs, it is estimated that tick-borne diseases costs between 50 and 3 100 billion dollars each year. The Center for Disease Control and Prevention currently recognizes 18 4 different tick-transmitted pathogens in the United States. This number is likely to rise as novel viruses 5 and pathogens are being discovered each year. One of these pathogens is Bourbon virus (BRBV), an 6 emerging tick-borne RNA virus that can infect and cause disease in humans. No antiviral therapies or 7 vaccines are available, highlighting the need to develop countermeasures against these life-threatening 8 diseases. The primary objective of this application is to develop an mRNA vaccine against BRBV, 9 evaluate its efficacy in vivo in a mouse model of BRBV and determine the mechanism of action. A 10 secondary objective is to evaluate different viral antigens and mRNA vaccine designs to improve 11 multivalent mRNA vaccines. Successful completion of the proposed studies will provide the preliminary 12 data for a R01 application aimed at developing a universal vaccine that confers protection against tick- 13 borne pathogens in the United States. 14 15