Please cite this article in press as: Gomes, H., et al., Vaccination with cyclin-dependent kinase tick antigen confers protection against Ixodes infestation. Vet. Parasitol. (2015), http://dx.doi.org/10.1016/j.vetpar.2015.05.022 ARTICLE IN PRESS G Model VETPAR-7645; No. of Pages 8 Veterinary Parasitology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar Vaccination with cyclin-dependent kinase tick antigen confers protection against Ixodes infestation Helga Gomes a, , Jorge Moraes a,f,g , Naftaly Githaka b , Renato Martins c , Masayoshi Isezaki d , Itabajara da Silva Vaz Jr. e,f , Carlos Logullo c,f , Satoru Konnai d , Kazuhiko Ohashi d a Laboratório Integrado de Bioquímica Hatisaburo Masuda, NUPEM UFRJ, Campus Macaé, Avenida São José do Barreto, São José do Barreto, Macaé, RJ CEP 27971–220, Brazil b Tick Vector Laboratory, International Livestock Research Institute, P.O. Box 30709-00100, Nairobi, Kenya c Laboratório de Química e Func ¸ ão de Proteínas e Peptídeos, Unidade de Experimentac ¸ ão Animal CBB UENF, Avenida Alberto Lamego, 2000, Horto, Campos dos Goytacazes RJ, CEP 28015–620, Brazil d Laboratory of Infectious Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo 060-0818, Japan e Centro de Biotecnologia e Faculdade de Veterinária, UFRGS, Avenida Bento Gonc ¸ alves, 9500, Porto Alegre, RS C.P. 15005, CEP 91501–970, Brazil f Instituto Nacional de Ciência e Tecnologia Entomologia Molecular, Rio de Janeiro, RJ, Brazil g Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, CCS, Bloco H, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil a r t i c l e i n f o Article history: Received 5 April 2015 Received in revised form 23 May 2015 Accepted 27 May 2015 Keywords: Tick Vaccine Ixodes persulcatus CDK Cell cycle a b s t r a c t Among arthropods, ticks lead as vectors of animal diseases and rank second to mosquitoes in transmitting human pathogens. Cyclin-dependent kinases (CDK) participate in cell cycle control in eukaryotes. CDKs are serine/threonine protein kinases and these catalytic subunits are activated or inactivated at specific stages of the cell cycle. To determine the potential of using CDKs as anti-tick vaccine antigens, hamsters were immunized with recombinant Ixodes persulcatus CDK10, followed by a homologous tick challenge. Though it was not exactly unexpected, IpCDK10 vaccination significantly impaired tick blood feeding and fecundity, which manifested as low engorgement weights, poor oviposition, and a reduction in 80% of hatching rates. These findings may underpin the development of more efficacious anti-tick vaccines based on the targeting of cell cycle control proteins. © 2015 Elsevier B.V. All rights reserved. 1. Introduction The Taiga tick, Ixodes persulcatus, is widespread across the Eurasian subcontinent and the Far East, where it transmits a variety of pathogens such as Borrelia burgdorferi, Babesia spp. and the tick- borne encephalitis virus (TBEV). This tick acquires disease-causing agents mainly through blood feeding, and multiple infections are common in ticks collected in the field (de la Fuente et al., 2008). In the northern Japanese island of Hokkaido, the combined effects of greater populations of sika deers and perhaps a warmer cli- mate have increased the prevalence of human infections vectored by I. persulcatus (Takano et al., 2014), requiring the adoption of enhanced tick control strategies. Previously, we described the presence of cyclin-dependent kinases (CDK) in the Rhipicephalus microplus tick (Gomes et al., 2013). These proteins participate in cell cycle control in eukaryotes. CDKs are serine/threonine protein kinases and these catalytic sub- Corresponding author. Tel.: +55 2221413945; fax: +55 2221413932. E-mail address: hgomes2@yahoo.com.br (H. Gomes). units are activated or inactivated at specific stages of the cell cycle. During its life cycle, the tick undergoes significant physiological changes. These are visible especially in tick females, for example, for which blood feeding may lead to a 100-fold body weight increase. These changes are likely to involve cell divisions and, consequently, are subject to CDKs regulation. Upon full engorgement, female ticks drop to the ground in order to digest the blood meal that supports oviposition (which may amount to 2000–20,000 eggs). Therefore, any intervention that halts cell cycle-dependent physiological pro- cesses may reduce tick numbers in the field and, therefore, mitigate problems associated with tick infestation and control. Vaccination against vector arthropods is an attractive alterna- tive to the use of the chemical acaricides conventionally used to control tick infestations (Parizi et al., 2012a; Merino et al., 2013). Anti-tick vaccines may lower tick numbers in the field, reducing disease transmission. Several classes of tick antigens have been evaluated in animal vaccine trials (Parizi et al., 2011, 2012b; Maritz-Olivier et al., 2012; Karasuyama and Yamanishi, 2014). In the tick, these proteins play a role in diverse biological functions, such as digestion, repro- duction, and development. More recently, Subolesin and Akirin http://dx.doi.org/10.1016/j.vetpar.2015.05.022 0304-4017/© 2015 Elsevier B.V. All rights reserved.