Targets of Acquired Tick-Resistance As Anti-Tick Vaccines

ABSTRACTThis proposal seeks to develop a novel vaccine against pathogens transmitted by
the blacklegged tick, Ixodes scapularis, by targeting tick salivary proteins (Salps) critical
for tick feeding. I. scapularis Salps provide functions critical for evading host defense
responses detrimental to the tick. Further, these salivary functions are also co-opted by
tick-transmitted pathogens to ensure their survival in the host. We reason that tick Salps
critical for tick feeding might serve as vaccine targets to impair tick feeding and
consequently, also thwart the transmission of multiple tick-borne pathogens.Our hypothesis is validated by the phenomenon of acquired tick-resistance
wherein, upon repeated tick infestations non-permissive hosts such as rabbits, and
guinea pigs mount a robust immune response against tick Salps critical for tick feeding
and this results in rapid rejection of ticks. Tick-resistance has also been shown to
prevent transmission of B. burgdorferi. Exploiting this phenomenon, we have identified
several Salps that are avidly recognized by tick-resistant animal sera.Since tick-resistant sera recognize multiple Salps it is reasonable to expect that
multiple immunodominant Salps might have to be targeted simultaneously to recapitulate
tick-resistance and achieve robust tick rejection. In this research study, we will:1. Assess the vaccine potential of a combination of immunodominant Salps to
prevent tick feeding in conjunction with adjuvants approved for human use.2. Examine the utility of simultaneously targeting multiple immunodominant tick
Salps to prevent the transmission of two tick-transmitted pathogens, B. burgdorferi and
A. phagocytophilum.This combination strategy targeting multiple Salps simultaneously has the
potential to result in a vaccine that might block the transmission of multiple I. scapularis-
borne pathogens.NARRATIVE
This Phase I proposal will develop a novel anti-I. scapularis vaccine by targeting
immunodominant tick salivary protein antigens to prevent tick feeding and consequently
impair the transmission of multiple I. scapularis-transmitted pathogens.