Abstract
Theileriosis poses a serious threat to ruminants in tropical and subtropical countries. It is a tick-borne disease, caused by an apicomplexan parasite, Theileria. The high disease burden in animals causes huge economic losses to marginal farmers. Further, with increasing cases of resistance to commonly used drugs, it is highly desirable to develop better and cost-effective vaccines against theileriosis. The only available vaccine, live attenuated parasite vaccine, has many drawbacks and hence is unsuitable for controlling this disease. Immuno-informatics has emerged as a useful tool in down selection of potential molecules for vaccine development. In this study, we have used an immuno-informatics driven genome-wide screening strategy to identify potential vaccine targets containing important and effective dominant immunogens against Theileria. The proteome of Theileria annulata was screened for proteins with probability of plasma membrane localization or GPI anchor. The proteins non-homologous to the host (bovine) were selected and their antigenicity was analyzed. The B-cell epitopes were identified in the selected proteins and mapped in the modeled structure of the proteins. A total of 19 linear epitopes in 12 proteins, exposed in the extracellular space and having the potential to induce protective antibodies were obtained. Additionally, CTL epitopes which are peptides with 9-mer core sequence, were also identified, modeled and docked with bovine MHC-I structures. The CTL epitopes showing high binding energy with the bovine MHC-I were further engineered in silico to design a putative multi-epitope vaccine candidate against Theileria parasites. The docking studies and molecular dynamics studies with the predicted multi-epitope vaccine candidate and modeled bovine TLR4 exhibited strong binding energy, suggesting that the complex is stable and the putative multi-epitope vaccine candidate can be a potentially good candidate for vaccine development.
Highlights
Theileria spp. are tick-borne protozoan parasites which belong to the subphylum apicomplexa which includes a number of other important pathogens such as Plasmodium, Babesia, Toxoplasma, Cryptosporidium, and Eimeria species
The results provide a strategy for epitopebased vaccine development for Theileria parasites and indicate that immuno-informatics could be an alternative strategy to rapidly discover potential antigens for subunit/multi-epitope vaccine development against parasites
A systematic workflow based on the immuno-informatics approach was designed to identify the potential vaccine candidates which would elicit an effective antibody response and to design a multi-epitope based vaccine candidate which would generate effective cell-mediated immune response against Theileria parasites (Figure 1A)
Summary
Theileria spp. are tick-borne protozoan parasites which belong to the subphylum apicomplexa which includes a number of other important pathogens such as Plasmodium, Babesia, Toxoplasma, Cryptosporidium, and Eimeria species. Theileria spp. are predominantly parasites of ruminants and are transmitted transstadially to the host by ticks [1, 2]. Among various species of these parasites, the most important ones include T. parva and T. annulata, which cause economically important diseases in cattle, east coast fever and tropical theileriosis, respectively. The indiscriminate use of acaricides has been leading to resistance in tick, adding another dimension to the problem. The chemotherapy agents such as parvaquone, buparvaquone, and halofuginone are effective during the initial stages of infection [6]. Some vaccinated cattle, especially immunocompromised cattle, remain as a source of transmission of parasites to other cattle [9]
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