A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis longicornis; cloning and preliminary assessment of its suitability as a candidate for a tick vaccine

Sugino, Maiko; Imamura, Saiki; Mulenga, Albert; Nakajima, Masahide; Tsuda, Akiko; Ohashi, Kazuhiko; Onuma, Misao

doi:10.1016/s0264-410x(03)00167-1

Cited by 84 publications

(80 citation statements)

References 28 publications

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“…HLS-1, another serpin-like antigen expressed in the midgut, inhibits the intrinsic pathway by an unknown mechanism. Vaccination of rabbits with recombinant HLS-1 resulted in 44% and 11% mortality of nymphs and adults, respectively [14]. These are the first examples of concealed tick anti-hemostatics as possible vaccine candidates.…”

Section: Thrombin Inhibitorsmentioning

confidence: 89%

Tick anti-hemostatics: targets for future vaccines and therapeutics

Maritz-Olivier

Stutzer

Jongejan

et al. 2007

Trends in Parasitology

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Section: Thrombin Inhibitorsmentioning

confidence: 89%

Tick anti-hemostatics: targets for future vaccines and therapeutics

Maritz-Olivier

Stutzer

Jongejan

et al. 2007

Trends in Parasitology

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“…Therefore, it is particular interesting to use serpins as anti-tick vaccine antigens because different members of this family of proteins are key regulators of either arthropod metabolism and/or host haemostasis. In addition, promising results have been reported using as vaccinating proteins serpins from other hard ticks A. hebraeum, A. variegatum, B. microplus, H. longicornis, and R. appendiculatus [16,[21][22][23] in their respective infestation models.…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous serpins could therefore interfere at the bite site with the regular immune, inflammatory and coagulation reactions from the host. Serpins have been recently isolated from the hard ticks Amblyomma hebraeum, Amblyomma variegatum, B. microplus, Haemaphysalis longicornis, Ixodes scapularis, and Rhipicephalus appendiculatus [16,[21][22][23]]. An example of the action of tick serpins on the host defence mechanisms is the protein HLS2 from H. longicornis which delays coagulation time and inhibits thrombin activity [16].…”

Section: Introductionmentioning

confidence: 99%

Protective immunity against Ixodes ricinus induced by a salivary serpin

Prévôt

Couvreur

Denis

et al. 2007

Vaccine

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Iris is a specific elastase inhibitor expressed in the salivary glands of the hard tick Ixodes ricinus. It belongs to the superfamily of serpins and interferes with both haemostasis and the immune response of the host. In this study, we first show that Iris is expressed in nymphs but not in the female midgut nor in males. We also show that Iris is present in the saliva. To examine its potency as anti-tick vaccine candidate, we set up three models of I. ricinus infestation on immunized animals: nymphs on mice, and adults and nymphs on rabbits. We report the rise of neutralizing antibodies following immunization of rabbits and mice. This comes with a significant protective immunity against ticks in rabbits only, resulting in a 30% mortality rate and a diminution of weight gain in both nymphs and adults and a prolongation of blood feeding time in adults. This is the first report on an anti-tick vaccine trial on I. ricinus using a protein able to interact with both host immunity and haemostasis, as a vaccinating antigen.

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“…A few serpins have been recently isolated from the hard ticks Amblyomma hebraeum, Amblyomma variegatum, Boophilus microplus, Hemaphysalis longicornis, I. scapularis, and Rhipicephalus appendiculatus (27)(28)(29)(30). These proteins are mainly expressed in tick salivary glands and are secreted in the saliva.…”

mentioning

confidence: 99%

Anti-hemostatic Effects of a Serpin from the Saliva of the Tick Ixodes ricinus

Prévôt

Adam

Boudjeltia

et al. 2006

Journal of Biological Chemistry

110

130

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Serpins (serine protease inhibitors) are a large family of structurally related proteins found in a wide variety of organisms, including hematophagous arthropods. Protein analyses revealed that Iris, previously described as an immunomodulator secreted in the tick saliva, is related to the leukocyte elastase inhibitor and possesses serpin motifs, including the reactive center loop (RCL), which is involved in the interaction between serpins and serine proteases. Only serine proteases were inhibited by purified recombinant Iris (rIris), whereas mutants L339A and A332P were found devoid of any protease inhibitory activity. The highest K a was observed with human leukocyteelastase, suggesting that elastase-like proteases are the natural targets of Iris. In addition, mutation M340R completely changed both Iris substrate specificity and affinity. This likely identified Met-340 as amino acid P1 in the RCL. The effects of rIris and its mutants were also tested on primary hemostasis, blood clotting, and fibrinolysis. rIris increased platelet adhesion, the contact phase-activated pathway of coagulation, and fibrinolysis times in a dose-dependent manner, whereas rIris mutant L339A affected only platelet adhesion. Taken together, these results indicate that Iris disrupts coagulation and fibrinolysis via the anti-proteolytic RCL domain. One or more other domains could be responsible for primary hemostasis inhibition. To our knowledge, this is the first ectoparasite serpin that interferes with both hemostasis and the immune response.Ticks are blood-sucking arthropods that infest a large variety of vertebrate hosts (mammals, birds, reptiles, and amphibians) in many parts of the world (1). To complete their blood meal, blood-sucking arthropods express a wide range of anti-hemostatic molecules in their saliva, including vasodilators, inhibitors of the platelet aggregation, and anti-coagulants (2). Tick saliva and salivary gland extracts are also known to modulate the host's defense mechanisms (3-6). Both anti-hemostatic and immunosuppressive compounds were identified, isolated, and characterized from soft and hard ticks. These compounds include histamine-binding proteins, tissue factor pathway inhibitor-like proteins, anti-thrombin-like proteins, and anticomplement factors (7-16).These last years, several laboratories reported the construction and screening of cDNA libraries from tick salivary glands. Thus, Das et al. (17) found 14 Ixodes scapularis immunodominant antigens, whereas Leboulle et al. (18) identified 27 mRNA, the expression of which is specifically induced or up-regulated during the Ixodes ricinus blood meal. Finally, Ribeiro and coworkers explored the sialome of the tick I. scapularis (19,20) and uncovered a large variety of putative bioactive agents. These studies all identified some serine protease inhibitors, containing serpin, kunitz, kazal, or ␣-macroglobulin motifs (21).To date, ϳ500 serpins have been identified in a large variety of species, including animals, viruses, and plants. On average, serpins are 35...

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A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis longicornis; cloning and preliminary assessment of its suitability as a candidate for a tick vaccine

Cited by 84 publications

References 28 publications

Tick anti-hemostatics: targets for future vaccines and therapeutics

Tick anti-hemostatics: targets for future vaccines and therapeutics

Protective immunity against Ixodes ricinus induced by a salivary serpin

Anti-hemostatic Effects of a Serpin from the Saliva of the Tick Ixodes ricinus

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