A Vaccinomics Approach for the Identification of Tick Protective Antigens for the Control of Ixodes ricinus and Dermacentor reticulatus Infestations in Companion Animals

Abstract

Ticks and tick-borne pathogens affect health and welfare of companion animals worldwide, and some human tick-borne diseases are associated with exposure to domestic animals. Vaccines are the most environmentally friendly alternative to acaracides for the control of tick infestations, and to reduce the risk for tick-borne diseases affecting human and animal health. However, vaccines have not been developed or successfully implemented for most vector-borne diseases. The main limitation for the development of effective vaccines is the identification of protective antigens. To address this limitation, in this study we used an experimental approach combining vaccinomics based on transcriptomics and proteomics data with vaccination trials for the identification of tick protective antigens. The study was focused on Ixodes ricinus and Dermacentor reticulatus that infest humans, companion animals and other domestic and wild animals, and transmit disease-causing pathogens. Tick larvae and adult salivary glands were selected for analysis to target tick organs and developmental stages playing a key role during tick life cycle and pathogen infection and transmission. Two I. ricinus (heme lipoprotein and uncharacterized secreted protein) and five D. reticulatus (glypican-like protein, secreted protein involved in homophilic cell adhesion, sulfate/anion exchanger, signal peptidase complex subunit 3, and uncharacterized secreted protein) proteins were identified as the most effective protective antigens based on the criteria of vaccine E > 80%. The putative function of selected protective antigens, which are involved in different biological processes, resulted in vaccines affecting multiple tick developmental stages. These results suggested that the combination of some of these antigens might be considered to increase vaccine efficacy through antigen synergy for the control of tick infestations and potentially affecting pathogen infection and transmission. These antigens were proposed for commercial vaccine development for the control of tick infestations in companion animals, and potentially in other hosts for these tick species.

De Novo Assembly and Analysis of Transcriptome of the Dermacentor Marginatus Genes Differentially Expressed After Blood Feeding and Long-term Starvation

“…5). Differentially expressed genes (DEGs) were almost one third of the overall unigenes and the down-regulated unigenes slightly outnumber up-regulated one between each compared groups indicating the three different states of D. marginatus female adults were experiencing signi cant physiological function shift which was in line with many Ixodidae transcriptome studies [19,26,44]. It is considered that H tick representing starved ticks experienced 6 months non-feeding period exhausting its energy sources of lipid, carbohydrate, and protein, whereasM tick stands for newly molted ticks that physiological status was at its prime with many of the energy metabolism-related genes down-regulated [26].…”

“…New antigens against a speci c tick species are still in need. Now screening of protective tick antigens revealed many potential tick protective antigens with omics approaches and tick vaccine trials [19]. On the other hand, researches focusing on biological process of tick blood feeding and reproduction has enhanced our knowledge on the functions of important tick molecules [20,21].…”

A Novel Combined Scientific and Artistic Approach for the Advanced Characterization of Interactomes: The Akirin/Subolesin Model

“…As shown previously by genetic approaches, musical ensembles supported the fact that AKR/SUB in different species are evolutionarily related and structurally conserved, and also predicted AKR2-protein interactions coinciding with those found by genetic approaches such as the Y2H screening used here. The methodological approach proposed here for quantum vaccinomics further advances the potential of the vaccinomics pipeline used before for the identification of candidate protective antigens [29,68,69]. Furthermore, if combined with network analysis for the integration of interactomics and regulomics datasets [70] and big data machine learning algorithms to identify candidate protective antigens and epitopes [71], quantum vaccinomics would result in designing chimeric antigens based on protective epitopes in SID from vector-and pathogen-derived regulatory proteins.…”

Vaccination with Ectoparasite Proteins Involved in Midgut Function and Blood Digestion Reduces Salmon Louse Infestations

“…Toll-like receptors (TLRs), such as TLR6 (P30), play an important role in the innate and adaptive immune responses to pathogens and are the target of new vaccine adjuvants by using lipopeptides that activate TLR2/6 heterodimers for use in Leishmania vaccines [48]. Potassium chloride and amino acid transporters and other solute carriers involved in cellular hypotonic salinity response and transmembrane transport, such as P33, have been used as candidate protective antigens in vaccine formulations against hard ticks (e.g., Aquaporin; [37][38][39][40]), soft ticks (e.g., ABC transporter; [37] and sulfate/anion exchanger; [49]) ticks and cat flea (e.g., zinc transporter ZIP13 homolog; [25]). Solute carriers, such as human solute carrier family 11 member 1 protein (SLC11A1), have been implicated in the control of bacterial replication and might influence the responses to vaccines with recombinant bacteria in different ways such as regulation of bacterial load or recombinant antigen dose, class II molecule expression, costimulatory or adjuvant activity, or antigen processing [50].…”