Identification of Ixodid Tick-Specific Aquaporin-1 Potential Anti-tick Vaccine Epitopes: An in-silico Analysis

Abstract

Ticks are arthropod vectors of pathogens of both Veterinary and Public health importance. Acaricide application, which is currently the mainstay of tick control, is hampered by high cost, the need for regular application and a selection of multi-acaricide resistant tick populations. In light of this, future tick control approaches are poised to rely on the integration of rational acaricide application and other methods, such as vaccination. To contribute to systematic research-guided efforts to produce anti-tick vaccines, we carried out an in-silico analysis of tick aquaporin-1 (AQP1) protein in order to identify tick-specific AQP1 peptide motifs that can be used in future peptide anti-tick vaccine development. We carried out multiple sequence alignment (MSA), motif analysis, homology modeling, and structural analysis to identify tick-specific AQP1 peptide motifs. BepiPred, Chou and Fasman-Turn, Karplus and Schulz Flexibility, and Parker-Hydrophilicity prediction models were used to predict these motifs' potential to induce B cell mediated immune responses. The tick AQP1 (GenBankID: QDO67142.1) protein was largely similar to the bovine AQP1 (PDB:1J4N) (23 % sequence similarity; Structural superimposition of the homology model and 14JN homotetramers gave an RMSD = 3.269 while superimposition of a single chain gave an RMSD = 1.475). Tick and bovine AQP1 transmembrane domains were largely similar while their extracellular and cytoplasmic domain loops showed variation. Two tick-specific AQP1 peptide motifs; M7 (residues 106–125, p = 5.4e-25), and M8 (residues 85–104, p = 3.3e-24) were identified. These two motifs are located on the extra-cellular AQP1 domain. Motifs; M7 and M8 showed the highest Parker-Hydrophilicity prediction immunogenicity scores of 1.784 and 1.536, respectively. These two motifs can be a good starting point for the development of potential tick AQP1 peptide-based anti-tick vaccines. Further analyses such as molecular dynamics, in vitro assays, and in vivo immunization assays are required to validate these findings.

Understanding Tick Biology and Its Implications in Anti-tick and Transmission Blocking Vaccines Against Tick-Borne Pathogens

“…Transcriptome studies of R. microplus showed that RmAQP1 as a potential vaccine antigen has significant amino acid sequence similarity to the human aquaporin 7 family and bovine AQP1 orthologs (64). This challenge can potentially be overcome by identifying highly conserved peptide motifs among tick AQP1 that differ from bovine and human AQP1 (65). It should be further tested against different tick species in different geographical regions.…”

Anti‐tick and pathogen transmission blocking vaccines

“…32,33 AQPs are integral membrane channels essential for water transport identified in tissues essential for water flux and help concentrate the blood meal in the midgut by selectively returning the water back to the host through the salivary gland. [34][35][36] Tick AQPs present as strong anti-tick vaccine candidates as, in contrast to other salivary proteins, AQP expression is found throughout tick life and feeding cycles, shows high sequence similarity across tick species, and is expressed throughout the entire length of the gut. [35][36][37][38] Disruption of tick osmoregulation by inhibiting AQP function can rapidly interfere with tick feeding, resulting in disruption of molting, viability and pathogen transmission.…”

“…[34][35][36] Tick AQPs present as strong anti-tick vaccine candidates as, in contrast to other salivary proteins, AQP expression is found throughout tick life and feeding cycles, shows high sequence similarity across tick species, and is expressed throughout the entire length of the gut. [35][36][37][38] Disruption of tick osmoregulation by inhibiting AQP function can rapidly interfere with tick feeding, resulting in disruption of molting, viability and pathogen transmission. Silencing of AQP using RNAi showed a 30% reduction of blood volume ingestion in Ixodes ricinus ticks, but did not cause detachment of ticks, 35 and reduced tick fitness with larval lethality in Rhipicephalus ( Boophilus) microplus ticks, with enhanced efficacy in calves infected with Babesia bovis compared to uninfected calves.…”

“…In order to regulate water flux during the feeding and salivation cycles, where approximately 75 per cent of ingested water in the blood meal is returned to the host in the saliva, 31 ticks use Aquaporins (AQPs), which have been molecularly well characterized in vertebrate and invertebrate species 32,33 . AQPs are integral membrane channels essential for water transport identified in tissues essential for water flux and help concentrate the blood meal in the midgut by selectively returning the water back to the host through the salivary gland 34‐36 . Tick AQPs present as strong anti‐tick vaccine candidates as, in contrast to other salivary proteins, AQP expression is found throughout tick life and feeding cycles, shows high sequence similarity across tick species, and is expressed throughout the entire length of the gut 35‐38 …”

Sequence identification and expression profile of seven Dermacentor marginatus glutathione S-transferase genes

“…B-cell epitope-based vaccines could induce a high specific immune response and induce longer immune protection (Ndawula et al 2020 ). Similar in silico analysis on tick-specific aquaporin-1 was carried out in the hope of finding specific epitopes vital to tick survival (Ndekezi et al 2019 ). The aim of the study was to obtain GST sequence information and identify highly antigenic GST expressed during blood feeding of female D. marginatus hoping to identify potential effective antigen which could be further tested for anti-tick vaccine trials.…”