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

Abstract

Ticks are obligate blood-feeding ectoparasites that transmit a wide variety of pathogens to animals and humans in many parts of the world. Currently, tick control methods primarily rely on the application of chemical acaricides, which results in the development of resistance among tick populations and environmental contamination. Therefore, an alternative tick control method, such as vaccines have been shown to be a feasible strategy that offers a sustainable, safe, effective, and environment-friendly solution. Nevertheless, novel control methods are hindered by a lack of understanding of tick biology, tick-pathogen-host interface, and identification of effective antigens in the development of vaccines. This review highlights the current knowledge and data on some of the tick-protective antigens that have been identified for the formulation of anti-tick vaccines along with the effects of these vaccines on the control of tick-borne diseases.

Keywords: Borrelia; Ixodes; anti-tick vaccines; blood; saliva; transmission-blocking.

Figure 1

A schematic representation of tick physiological processes and involved molecules tested as vaccine candidates [modified from (78, 103)]. The most promising vaccine candidates are underlined. The red arrow represents blood meal uptake, and the blue arrow represents saliva injection. Several tick protease inhibitor families have been reported in the salivary glands and implicated in both tick biology/physiology. Major blood digestive enzymes (cathepsin B, C, D, L, and Legumain), blood digestion, heme/iron metabolism, detoxification, and inter-tissue transport that may serve as rational targets for “anti-tick” intervention. SG, salivary glands; MG, midgut; OV, ovary; HLS2, Haemaphysalis longicornis serpin-2; RAS-1,2,3,4, Rhipicephalus appendiculatus; IRIS, Ixodes ricinus immunosuppressor; Sialostatin L, Ixodes scapularis; OmC2, Ornithodoros moubata; Metis-1, metalloproteases from Ixodes ricinus; BrRm-MP4, metalloproteases Rhipicephalus (Boophilus) microplus; HLMP1, Haemaphysalis longicornis metalloprotease.

Figure 2

A proposed model for the hemoglobinolytic pathway in I. ricinus [modified from (75)]. The enzymes are color-coded according to clan membership- AA clan aspartic peptidases (red), CD clan cysteine peptidases (purple), CA clan (papain family) cysteine peptidases (green), and serine and metallopeptidases (black). The endopeptidases, cathepsin D (CatD) supported by cathepsin L (CatL) and legumain (AE), are responsible for the primary cleavage of hemoglobin. The production of secondary small fragments is dominated by the endopeptidase activity of cathepsin B (CatB). Exopeptidases act on the peptides released by the action of the endopeptidases through the carboxy-dipeptidase activity of CatB and the amino-dipeptidase activity of cathepsin C (CatC). Monopeptidases, including leucine aminopeptidase (LAP) and serine carboxypeptidase (SCP), might participate in the liberation of free amino acids.

Figure 3

A schematic representation of the integrative reverse vaccinology approach toward vaccine development.