Understanding the Complexity of Ixodes Scapularis and Amblyomma Americanum Tick Feeding Through Proteomics for a Multi-Antigen Vaccine Design

Tick saliva proteins facilitate feeding success and transmission of tick-borne disease agents by ticks, and thus, they might serve as effective antigens for a tick vaccine. This dissertation for the first-time identifies saliva proteins that are secreted every 24 h during tick-feeding of two distantly-related and most medically important ticks species in the United States, Ixodes scapularis and Amblyomma americanum. Data in this dissertation reveal that tick feeding is a complex system that is dynamically changing in response to the host defenses. Understanding biological functional roles of tick saliva proteins is critical to developing novel methods to prevent tick-borne disease infections. Therefore, the second part of this dissertation defines the functional roles of three serine protease inhibitors (serpins: AAS19, AAS41 and AAS46), which are thought to control serine proteases that mediate host defense mechanisms. While these serpins are secreted into the host during feeding and are immunogenic, only AAS19 and AAS41 were functionally active, having anti-hemostatic or anti-inflammatory properties, respectively. The finding that despite being 97% identical to AAS41, AAS46 is apparently not an efficient inhibitor provides insights into how the tick might evade host defenses: it is possible that ticks secrete AAS46 as an immune decoy to protect the functional AAS41 from immune attack. Finally, information generated from this dissertation was utilized to formulate a cocktail anti-tick vaccine that included 13 recombinant tick saliva proteins. Although these antigens elicited an immune response in immunized cattle, they did not protect cattle against primary tick infestations; however, immunization enhanced the naturally acquired immunity against tick feeding that is elicited by repeated infestation. This dissertation contributes to a better understanding of the molecular basis of tick-feeding physiology, which is the needed first step before novel tick control methods can be developed. Results from this dissertation have contributed to our understanding of the molecular basis of tick feeding physiology and will serve as foundation to formulate an effective tick-antigen based vaccine to prevent tick-borne disease transmission