Anti-tick vaccines have the potential to be an environmentally friendly and cost-effective option for tick control. In vaccine development, the identification of efficacious antigens forms the major bottleneck. In this study, the efficacy of immunization with recombinant ferritin 2 and native tick protein extracts (TPEs) against Ixodes ricinus infestations in calves was assessed in two immunization experiments. In the first experiment, each calf (n = 3) was immunized twice with recombinant ferritin 2 from I. ricinus (IrFER2), TPE consisting of soluble proteins from the internal organs of partially fed I. ricinus females, or adjuvant, respectively. In the second experiment, each calf (n = 4) was immunized with protein extracts from the midgut (ME) of partially fed females, the salivary glands (SGE) of partially fed females, a combination of ME and SGE, or adjuvant, respectively. Two weeks after the booster immunization, calves were challenged with 100 females and 200 nymphs. Blood was collected from the calves before the first and after the second immunization and fed to I. ricinus females and nymphs using an in vitro artificial tick feeding system. The two calves vaccinated with whole TPE and midgut extract (ME) showed hyperemia on tick bite sites 2 days post tick infestation and exudative blisters were observed in the ME-vaccinated animal, signs that were suggestive of a delayed type hypersensitivity (DTH) reaction. Significantly fewer ticks successfully fed on the three animals vaccinated with TPE, SGE, or ME. Adults fed on the TPE and ME vaccinated animals weighed significantly less. Tick feeding on the IrFER2 vaccinated calf was not impaired. The in vitro feeding of serum or fresh whole blood collected from the vaccinated animals did not significantly affect tick feeding success. Immunization with native I. ricinus TPEs thus conferred a strong immune response in calves and significantly reduced the feeding success of both nymphs and adults. In vitro feeding of serum or blood collected from vaccinated animals to ticks did not affect tick feeding, indicating that antibodies alone were not responsible for the observed vaccine immunity.

Center for Cooperative Research in Biosciences Derio Spain

Center for Experimental and Molecular Medicine Academic Medical Center University of Amsterdam Amsterdam Netherlands

Ikerbasque Basque Foundation for Science Bilbao Spain

Institute for Parasitology and Tropical Veterinary Medicine Freie Universität Berlin Berlin Germany

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czechia

Institute of Veterinary Pathology Freie Universität Berlin Berlin Germany

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Allen J. R., Humphreys S. J. (1979). Immunisation of guinea pigs and cattle against ticks. PubMed DOI

Almazan C., Blas-Machado U., Kocan K. M., Yoshioka J. H., Blouin E. F., Mangold A. J., et al. (2005). Characterization of three PubMed DOI

Banerjee D. P., Kumar R., Kumar S., Sengupta P. P. (2003). Immunization of crossbred cattle ( PubMed DOI

Brei B., Brownstein J. S., George J. E., Pound J. M., Miller J. A., Daniels T. J., et al. (2009). Evaluation of the United States department of agriculture northeast area-wide tick control project by meta-analysis. PubMed DOI PMC

Brown S. J. (1988). Evidence for regurgitation by PubMed DOI

Burgdorfer W., Hayes S. F., Corwin D. (1989). Pathophysiology of the Lyme disease spirochete, PubMed DOI

Contreras M., Alberdi P., Fernandez, De Mera I. G., Krull C., Nijhof A., et al. (2017). Vaccinomics approach to the identification of candidate protective antigens for the control of tick vector infestations and PubMed DOI PMC

Contreras M., de la Fuente J. (2017). Control of infestations by PubMed DOI

Coumou J., Wagemakers A., Trentelman J. J., Nijhof A. M., Hovius J. W. (2015). Vaccination against Bm86 Homologues in rabbits does not impair PubMed DOI PMC

de Vos S., Zeinstra L., Taoufik O., Willadsen P., Jongejan F. (2001). Evidence for the utility of the Bm86 antigen from PubMed DOI

Decrem Y., Mariller M., Lahaye K., Blasioli V., Beaufays J., Zouaoui Boudjeltia K., et al. (2008). The impact of gene knock-down and vaccination against salivary metalloproteases on blood feeding and egg laying by PubMed DOI

Essuman S., Dipeolu O. O., Odhiambo T. R. (1991). Immunization of cattle with a semi-purified fraction of solubilized membrane-bound antigens extracted from the midgut of the tick DOI

Fulop B., Poggensee G. (2008). Epidemiological situation of Lyme borreliosis in Germany: surveillance data from six Eastern German States, 2002 to 2006. PubMed DOI

Gillet L., Schroeder H., Mast J., Thirion M., Renauld J. C., Dewals B., et al. (2009). Anchoring tick salivary anti-complement proteins IRAC I and IRAC II to membrane increases their immunogenicity. PubMed DOI PMC

Gomes H., Moraes J., Githaka N., Martins R., Isezaki M., Vaz Ida S., et al. (2015). Vaccination with cyclin-dependent kinase tick antigen confers protection against Ixodes infestation. PubMed DOI

Gray J. S., Kahl O., Robertson J. N., Daniel M., Estrada-Pena A., Gettinby G., et al. (1998). Lyme borreliosis habitat assessment. PubMed DOI

Hajdusek O., Almazan C., Loosova G., Villar M., Canales M., Grubhoffer L., et al. (2010). Characterization of ferritin 2 for the control of tick infestations. PubMed DOI

Hajdusek O., Sojka D., Kopacek P., Buresova V., Franta Z., Sauman I., et al. (2009). Knockdown of proteins involved in iron metabolism limits tick reproduction and development. PubMed DOI PMC

Jongejan F., Pegram R. G., Zivkovic D., Hensen E. J., Mwase E. T., Thielemans M. J., et al. (1989). Monitoring of naturally acquired and artificially induced immunity to PubMed DOI

Kemp D. H., Pearson R. D., Gough J. M., Willadsen P. (1989). Vaccination against PubMed DOI

Kimaro E. E., Opdebeeck J. P. (1994). Tick infestations on cattle vaccinated with extracts from the eggs and the gut of PubMed DOI

Kotsyfakis M., Anderson J. M., Andersen J. F., Calvo E., Francischetti I. M., Mather T. N., et al. (2008). Cutting edge: immunity against a “silent” salivary antigen of the Lyme vector PubMed DOI PMC

Krober T., Guerin P. M. (2007). In vitro feeding assays for hard ticks. PubMed DOI

Krull C., Bohme B., Clausen P. H., Nijhof A. M. (2017). Optimization of an artificial tick feeding assay for PubMed DOI PMC

Manzano-Roman R., Encinas-Grandes A., Perez-Sanchez R. (2006). Antigens from the midgut membranes of PubMed DOI

Nijhof A. M., Taoufik A., De La Fuente J., Kocan K. M., De Vries E., Jongejan F. (2007). Gene silencing of the tick protective antigens, Bm86, Bm91 and subolesin, in the one-host tick PubMed DOI PMC

Nikpay A., Nabian S. (2016). Immunization of cattle with tick salivary gland extracts. PubMed PMC

Opdebeeck J. P., Daly K. E. (1990). Immune responses of infected and vaccinated Hereford cattle to antigens of the cattle tick, PubMed DOI

Parizi L. F., Githaka N. W., Logullo C., Konnai S., Masuda A., Ohashi K., et al. (2012). The quest for a universal vaccine against ticks: cross-immunity insights. PubMed DOI

Perner J., Provaznik J., Schrenkova J., Urbanova V., Ribeiro J. M., Kopacek P. (2016). RNA-seq analyses of the midgut from blood- and serum-fed PubMed DOI PMC

Pound J. M., Lohmeyer K. H., Davey R. B., Miller J. A., George J. E. (2012). Efficacy of amitraz-impregnated collars on white-tailed deer (Artiodactyla: Cervidae) in reducing free-living populations of lone star ticks (Acari: Ixodidae). PubMed DOI

Prevot P. P., Couvreur B., Denis V., Brossard M., Vanhamme L., Godfroid E. (2007). Protective immunity against PubMed DOI

Radzisauskiene D., Zagminas K., Asokliene L., Jasionis A., Mameniskiene R., Ambrozaitis A., et al. (2018). Epidemiological patterns of tick-borne encephalitis in Lithuania and clinical features in adults in the light of the high incidence in recent years: a retrospective study. PubMed DOI PMC

Randolph S. E., Green R. M., Hoodless A. N., Peacey M. F. (2002). An empirical quantitative framework for the seasonal population dynamics of the tick PubMed DOI

Rechav Y., Spickett A. M., Dauth J., Tembo S. D., Clarke F. C., Heller-Haupt A., et al. (1992). Immunization of guinea-pigs and cattle against adult PubMed PMC

Schwartz A. M., Hinckley A. F., Mead P. S., Hook S. A., Kugeler K. J. (2017). Surveillance for Lyme disease – United States, 2008-2015. PubMed DOI PMC

Schwarz A., Tenzer S., Hackenberg M., Erhart J., Gerhold-Ay A., Mazur J., et al. (2014). A systems level analysis reveals transcriptomic and proteomic complexity in PubMed DOI PMC

Sharma S., Hinds L. A. (2012). Formulation and delivery of vaccines: ongoing challenges for animal management. PubMed DOI PMC

Smith R., Takkinen J. (2006). Lyme borreliosis: Europe-wide coordinated surveillance and action needed? PubMed

Sonenshine D. E., Anderson J. M. (2014). “Mouthparts and digestive system: anatomy and molecular biology of feeding and digestion,” in

Sprong H., Azagi T., Hoornstra D., Nijhof A. M., Knorr S., Baarsma M. E., et al. (2018). Control of Lyme borreliosis and other PubMed DOI PMC

Sprong H., Trentelman J., Seemann I., Grubhoffer L., Rego R. O., Hajdusek O., et al. (2014). ANTIDotE: anti-tick vaccines to prevent tick-borne diseases in Europe. PubMed DOI PMC

Sykes R. A., Makiello P. (2017). An estimate of Lyme borreliosis incidence in Western Europe. PubMed DOI

Szabo M. P., Bechara G. H. (1997). Immunisation of dogs and guinea pigs against PubMed DOI

Trager W. (1939a). Acquired immunity to ticks. DOI

Trager W. (1939b). Further observations on acquired immunity to the tick DOI

Trimnell A. R., Davies G. M., Lissina O., Hails R. S., Nuttall P. A. (2005). A cross-reactive tick cement antigen is a candidate broad-spectrum tick vaccine. PubMed DOI

Valenzuela J. G., Belkaid Y., Garfield M. K., Mendez S., Kamhawi S., Rowton E. D., et al. (2001). Toward a defined anti- PubMed DOI PMC

Willadsen P. (2004). Anti-tick vaccines. PubMed DOI

Willadsen P., Riding G. A., Mckenna R. V., Kemp D. H., Tellam R. L., Nielsen J. N., et al. (1989). Immunologic control of a parasitic arthropod. Identification of a protective antigen from PubMed

Wolfensohn S., Lloyd M. (2013).

Wong J. Y., Opdebeeck J. P. (1989). Protective efficacy of antigens solubilized from gut membranes of the cattle tick, PubMed PMC

Zweygarth E., Just M. C., De Waal D. T. (1995). Continuous in vitro cultivation of erythrocytic stages of PubMed DOI

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