In the United States reported human vector-borne diseases are primarily tick-borne. For continued cycling of tick-borne disease pathogens in nature, successful tick feeding is required. Molecular mechanisms that regulate early stage tick feeding are poorly defined. They are critical to understanding the acquisition and transmission of pathogens by ticks, which in turn will be important in designing novel approaches to control ticks and tick- borne diseases. The goal of this proposal is molecular identification and target validation of Amblyomma americanum tick saliva proteins that are injected into the host during the first 48 h of tick feeding. The rationale to focus on this time point is that, it precedes the key facets of tick feeding, blood meal up take and tick borne disease agent transmission. The hypothesis is that tick saliva proteins critical to feeding success and pathogen infection of the host are injected into the host during the first 48 h of feeding and blocking their functions will protect animals against tick feeding and pathogen infection. This hypothesis is based on preliminary experimental evidence that repeated tick infestation of rabbits for 48 h with nymph or adult ticks conferred protective tick immunity as revealed by mortality failure of ticks to attach or remain attached onto host skin. Previous efforts to confer protective tick immunity by immunizing animals with single tick saliva recombinant proteins have produced mixed results. In this research we have proposed a previously unexplored approach, to immunize animals against tick feeding with multi-epitope chimeric tick saliva protein vaccine antigens. The idea is that immunity to these chimeric antigens will mimic protective tick immunity conferred tick saliva protein antigens during repeated infestations. There are 3 specific aims. The first is to clone cDNAs that encode A. americanum tick saliva proteins that are injected into the host during the first 48 h of tick feeding. The second is to validate immunogenicity of putative antigenic peptide regions in tick saliva proteins. Validated immunogenic peptides will represent tick saliva protein regions that mediate tick resistance in repeated tick feeding and will thus represent potential tick vaccine antigens. The third is to validate tick immunity and anamnestic antibody response of immunogenic peptide-cocktail immunized rabbits to tick infestation. The rationale is that if immunization of rabbits with immunogenic peptide-cocktails confers tick immunity that is comparable to that in repeated tick infestation, data from this application will set the foundation to design chimeric tick saliva proteins.
In the United States ticks transmit more vector borne disease agents than any other vector arthropod. Limitations associated with current acaricide based tick control strategies that threaten the future sustainability of containment programs for tick borne illnesses, have necessitated the need for development of alternative tick control strategies. Identification of important tick proteins that regulate tick physiology and facilitate tick feeding is important before alternative tick control methods can be developed.
|Bakshi, Mariam; Kim, Tae Kwon; Mulenga, Albert (2018) Disruption of blood meal-responsive serpins prevents Ixodes scapularis from feeding to repletion. Ticks Tick Borne Dis 9:506-518|
|Hollmann, Taylor; Kim, Tae Kwon; Tirloni, Lucas et al. (2018) Identification and characterization of proteins in the Amblyomma americanum tick cement cone. Int J Parasitol 48:211-224|
|Tirloni, Lucas; Kim, Tae K; Pinto, Antônio F M et al. (2017) Tick-Host Range Adaptation: Changes in Protein Profiles in Unfed Adult Ixodes scapularis and Amblyomma americanum Saliva Stimulated to Feed on Different Hosts. Front Cell Infect Microbiol 7:517|
|Radulovi?, Željko M; Mulenga, Albert (2017) Heparan sulfate/heparin glycosaminoglycan binding alters inhibitory profile and enhances anticoagulant function of conserved Amblyomma americanum tick saliva serpin 19. Insect Biochem Mol Biol 80:1-10|
|Porter, Lindsay M; Radulovi?, Željko M; Mulenga, Albert (2017) A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses. Parasit Vectors 10:152|
|Kim, Tae Kwon; Tirloni, Lucas; Pinto, Antônio F M et al. (2016) Ixodes scapularis Tick Saliva Proteins Sequentially Secreted Every 24 h during Blood Feeding. PLoS Negl Trop Dis 10:e0004323|
|Kim, Tae K; Radulovic, Zeljko; Mulenga, Albert (2016) Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19. Ticks Tick Borne Dis 7:405-14|
|Tirloni, Lucas; Kim, Tae Kwon; Coutinho, Mariana Loner et al. (2016) The putative role of Rhipicephalus microplus salivary serpins in the tick-host relationship. Insect Biochem Mol Biol 71:12-28|
|Kim, Tae Kwon; Tirloni, Lucas; Radulovic, Zeljko et al. (2015) Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions. Int J Parasitol 45:613-27|
|Lewis, Lauren A; Radulovi?, Željko M; Kim, Tae K et al. (2015) Identification of 24h Ixodes scapularis immunogenic tick saliva proteins. Ticks Tick Borne Dis 6:424-34|
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