Ixodes scapularis, commonly known as the deer tick, is the predominant tick vector of several human pathogens including Borrelia burgdorferi, the Lyme disease agent and transmits the harbored pathogens to the host during feeding. Vaccines against these tick-borne pathogens are not available. Thisproposalwillexamineanewparadigmthatsuggestsacriticalroleforticksalivaryglycans in provoking immune responses in the host critical to thwart tick feeding. This study will set the tone for the development of tick salivary glycan-based vaccines to block tick feeding and prevent transmissionofmultipletick-transmittedpathogenstothehost. William Trager?s seminal observation showed that repeated tick infestations of non-permissive hostssuchasguineapigsandrabbitsprovokeabriskhumoralimmuneresponsedirectedagainstcritical tick salivary components that results in thwarting tick feeding ? a phenomenon referred to as acquired tick-resistance.Ourinitialobservationsdemonstratethatglycosylationsonsecretedticksalivaryproteins play a significant role in eliciting tick-resistance in guinea pigs. Glycans or carbohydrates decorations present on several tick salivary proteins likely maintain the structure and function of the protein. These glycan decorations potentially serve as ?vector-associated-molecular patterns? (VAMPs) and elicit glycan-specificimmuneresponsesthatresultintickrejection.Todevelopthisconceptandtodetermine theroleofticksalivaryglycansinthecontextoftick-hostinteractionswewill: A.Identifyimmunogenicsalivaryglycanstargetedbytick-resistantguineapigsera. B.Identifysalivaryglycoproteinsthatcontainimmunogenicglycans. C. Determine if immunization of guinea pigs with the glycans or glycoproteins might provoke tick- resistance and consequently thwart tick feeding and prevent pathogen transmission. We will use B. burgdorferiasanexampleofatick-transmittedpathogen. Theresultsofthiseffortwillilluminateanewfacetofticksalivaryproteins?theglycansthat decoratetheproteinsandtheroleoftheseglycansinmodulatinghostimmunityandoffernew approachestoimpairtickfeedingandpreventpathogentransmission.

Public Health Relevance

The goal of this effort is to define immunogenic tick salivary glycans that elicit immune responses critical for thwarting tick feeding and consequent pathogen transmission. This study will reveal a less understood facet of tick saliva and provide the preamble for the design of salivary glycan-based anti-tick vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI128182-01A1
Application #
9386568
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Ilias, Maliha R
Project Start
2017-06-01
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
$221,875
Indirect Cost
$84,375
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520