Tick-Encoded Serine Proteinase Inhibitors (Serpins); Potential Target Antigens for Tick Vaccine Development.

Abstract

ABSTRACT. Immunological protection of hosts against tick infestation is at present the most practically sustainable alternative tick control method to the current use of acaricides that is riddled with serious limitations. The current focus of tick vaccine research is the identification, cloning and in vitro production of recombinant tick vaccine candidate antigens. We have examined a selected number of reports on the roles of parasite-encoded members of the serine proteinase inhibitor (serpin) superfamily in modulation of mammalian anti-parasite defense and developed some food for thought commentaries on the possibility of targeting this class of proteins for anti-tick vaccine development. KEY WORDS: ixodid tick, serpin, tick vaccine development.J. Vet. Med. Sci. 63(10): 1063-1069 Ixodid ticks are the most important blood feeding arthropod vectors of infectious agents to domestic livestock and wild animals, and they are second to mosquitoes as vectors of pathogens to man [37]. The livestock industry annually experiences monetary loses estimated in hundreds of millions of dollars due to direct tick feeding activities and the diseases they transmit. Suppression of tick populations remains the method of choice to reduce the tick impact on the livestock industry. Tick control is at present almost totally dependent on the use of acaricides. Limitations of this approach, such as ixodid ticks developing resistance to these chemicals and acaricidal contamination of the environment have stimulated research into alternative methods to control ticks. Among the several methods that have been considered so far [50], vaccination of hosts against ticks has been shown to be practical and sustainable. This was evidenced in a series of studies [42,57,61] leading to commercialization [62] of the first ever anti-arthropod vaccine against the cattle tick Boophilus microplus. While work on the anti-B. microplus tick vaccine is remarkably advanced and practical, studies on other major tick species such as Amblyomma, Hyalomma and Rhipicephalus are still far from being practical [30]. The focus of research in tick vaccine development at present is the identification, molecular cloning, in vitro production and characterization of tick proteins responsible for executing key roles such as acquisition and digestion of the blood meal, modulation of host immune response and pathogen transmission by ticks [30]. Figure 1 summarizes the postulated effect of tick saliva proteins on the host's immune response factors. During the long feeding periods, hard ticks provoke host immune defense which is aimed at expelling the intruding tick. In order to complete feeding successfully, ticks secrete an array of bioactive saliva proteins which modulate the host's homeostatic balance. Additionally tick gut proteins are also essential in ensuring that the imbibed blood remains in a fluid sate and available for digestion [21]. The authors of this review previously cloned and expressed in vitro two cDNAs encoding immunodominant 29 (p29) and 34 kDa (HL34) sali...

Gut transcriptome analysis on females of Ornithodoros mimon (Acari: Argasidae) and phylogenetic inference of ticks

“…However, other authors have suggested that inhibitors such as serpin can be used by ticks to regulate endopeptidase activity and hemostasis (MULENGA et al, 2001(MULENGA et al, , 2003PERNER et al, 2016;TIRLONI et al, 2014). Peptidase inhibitors have been mentioned as effective antigens for preparing vaccines, because these genes are essential for the survival of ticks, since they are associated with endogenous processes such as regulation of hemolymph coagulation through controlling proteinase activity (IMAMURA et al, 2005).…”

Molecular and expression analysis of a family of the Amblyomma americanum tick Lospins

“…Given the importance of serpins in the regulation of mammalian host's physiological processes, it was hypothesized that ticks might encode serpins to evade host defense, and that blocking their function via immunization would compromise the tick's ability to feed (Mulenga et al, 2001;Mulenga et al, 2003). Indeed, a limited number of studies have reported mortality and reduced feeding efficiency in Ixodes ricinus Say (Prevot et al, 2007), Haemaphysalis longicornis Neuman (Sugino et al, 2003;Imamura et al, 2005) and Rhipicephalus appendiculatus Neuman (Imamura et al, 2005) ticks that fed on recombinant-serpin-immunized hosts.…”

Amblyomma americanum (L.) (Acari: Ixodidae) tick salivary gland serine protease inhibitor (serpin) 6 is secreted into tick saliva during tick feeding

“…In hypothesizing that tick-encoded serpins play key role(s) in regulating the evasion of host defense reactions by ticks (Prevot et al, 2007;Mulenga et al, 2001a;Mulenga et al, 2003;Mulenga et al, 2008, Mulenga et al, 2009, the underlying assumption is that ticks inject serpins into the host during tick feeding. In previous studies the basis for this assumption has been the expression of K. C. Chalaire and others Mr (kDa) RP 1 putatively extracellular serpin mRNA in tick salivary glands (Prevot et al, 2007;Prevot et al, 2006;Mulenga et al, 2003;Mulenga et al, 2008;Mulenga et al, 2009).…”

“…To complete feeding, ticks secrete enzymes that block inflammation and blood clotting, thus ensuring continued blood flow to the feeding site (Nuttall et al, 2006). Given that the host's primary lines of defense to tick feeding activity, inflammation and blood coagulation, are serine protease-mediated pathways that are regulated by serpins (Huntington, 2006;Gettins, 2002), it has been hypothesized that ticks may use serpins to evade the host's immune response (Mulenga et al, 2001a). An increasing number of serpin-encoding cDNAs have been identified in several tick species of medical and veterinary importance, including A. americanum (Mulenga et al, 2007), Haemaphysalis longicornis (Mulenga et al, 2001b;Imamura et al, 2005;Sugino et al, 2003), Ixodes ricinus (Prevot et al, 2006), I. scapularis (Mulenga et al, 2009) and Rhiphicephalus appendiculatus Imamura et al, 2006;Imamura et al, 2008).…”