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      Preliminary Evaluation of Tick Protein Extracts and Recombinant Ferritin 2 as Anti-tick Vaccines Targeting Ixodes ricinus in Cattle

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          Abstract

          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.

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          Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens

          Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351–1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell–deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
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            Surveillance for Lyme Disease — United States, 2008–2015

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              An empirical quantitative framework for the seasonal population dynamics of the tick Ixodes ricinus.

              The wide geographic and climatic range of the tick Ixodes ricinus, and the consequent marked variation in its seasonal population dynamics, have a direct impact on the transmission dynamics of the many pathogens vectored by this tick species. We use long-term observations on the seasonal abundance and fat contents (a marker of physiological ageing) of ticks, and contemporaneous microclimate at three field sites in the UK, to establish a simple quantitative framework for the phenology (i.e. seasonal cycle of development) of I. ricinus as a foundation for a generic population model. An hour-degree tick inter-stadial development model, driven by soil temperature and including diapause, predicts the recruitment (i.e. emergence from the previous stage) of a single cohort of each stage of ticks each year in the autumn. The timing of predicted emergence coincides exactly with the new appearance of high-fat nymphs and adults in the autumn. Thereafter, fat contents declined steadily until unfed ticks with very low energy reserves disappeared from the questing population within about 1 year from their recruitment. Very few newly emerged ticks were counted on the vegetation in the autumn, but they appeared in increasing numbers through the following spring. Larger ticks became active and subsequently left the questing population before smaller ones. Questing tick population dynamics are determined by seasonal patterns of tick behaviour, host-contact rates and mortality rates, superimposed on a basal phenology that is much less complex than has hitherto been portrayed.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                05 December 2018
                2018
                : 9
                : 1696
                Affiliations
                [1] 1Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin , Berlin, Germany
                [2] 2Center for Cooperative Research in Biosciences (CIC bioGUNE) , Derio, Spain
                [3] 3Ikerbasque, Basque Foundation for Science , Bilbao, Spain
                [4] 4Institute of Parasitology, Biology Centre, Czech Academy of Sciences , České Budějovice, Czechia
                [5] 5Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam , Amsterdam, Netherlands
                [6] 6Institute of Veterinary Pathology, Freie Universität Berlin , Berlin, Germany
                Author notes

                Edited by: Itabajara Da Silva Vaz Jr., Universidade Federal do Rio Grande do Sul (UFRGS), Brazil

                Reviewed by: Lucas Tirloni, National Institute of Allergy and Infectious Diseases (NIAID), United States; Adriana Seixas, Federal University of Health Sciences of Porto Alegre, Brazil

                *Correspondence: Ard M. Nijhof, ard.nijhof@ 123456fu-berlin.de

                This article was submitted to Invertebrate Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.01696
                6290058
                a9af78dd-7c3f-4ddd-aa2a-250155989432
                Copyright © 2018 Knorr, Anguita, Cortazar, Hajdusek, Kopáček, Trentelman, Kershaw, Hovius and Nijhof.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 August 2018
                : 12 November 2018
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 53, Pages: 11, Words: 0
                Funding
                Funded by: Seventh Framework Programme 10.13039/100011102
                Funded by: Grantová Agentura České Republiky 10.13039/501100001824
                Funded by: Bundesministerium für Bildung und Forschung 10.13039/501100002347
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                ixodes ricinus,anti-tick vaccine,salivary glands extract,midgut extract,ferritin,artificial tick feeding

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