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      Vaccination of cattle with synthetic peptides corresponding to predicted extracellular domains of Rhipicephalus (Boophilus) microplus aquaporin 2 reduced the number of ticks feeding to repletion

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          Abstract

          Background

          There have been ongoing efforts to identify anti-tick vaccine targets to protect cattle from infestation with cattle fever ticks Rhipicephalus ( Boophilus) microplus. Two commercial vaccines based on the tick gut protein Bm86 have had variable effectiveness, which has led to poor acceptance, and numerous studies have attempted to identify vaccine antigens that will provide more consistently effective protection. Transcriptomic analysis of R. microplus led to identification of three aquaporin genes annotated to code for transmembrane proteins involved in the transport of water across cell membranes. Previous work showed that vaccination with full-length recombinant aquaporin 1 (RmAQP1) reduced tick burdens on cattle. Targeted silencing of aquaporin 2 (RmAQP2) expression suggested it might also be a good anti-tick vaccination target.

          Methods

          Three synthetic peptides from the predicted extracellular domains of RmAQP2 were used to vaccinate cattle. Peptides were conjugated to keyhole limpet hemocyanin (KLH) as an antigenic carrier molecule. We monitored the antibody response with ELISA and challenged vaccinated cattle with R. microplus larvae.

          Results

          There was a 25% reduction overall in the numbers of ticks feeding to repletion on the vaccinated cattle. Immune sera from vaccinated cattle recognized native tick proteins on a western blot and reacted to the three individual synthetic peptides in an ELISA. The vaccinated calf with the highest total IgG titer was not the most effective at controlling ticks; ratios of IgG isotypes 1 and 2 differed greatly among the three vaccinated cattle; the calf with the highest IgG1/IgG2 ratio had the fewest ticks. Ticks on vaccinated cattle had significantly greater replete weights compared to ticks on controls, mirroring results seen with RNA silencing of RmAQP2. However, protein data could not confirm that vaccination had any impact on the ability of the tick to concentrate its blood meal by removing water.

          Conclusions

          A reduced number of ticks feed successfully on cattle vaccinated to produce antibodies against the extracellular domains of RmAQP2. However, our predicted mechanism, that antibody binding blocks the ability of RmAQP2 to move water out of the blood meal, could not be confirmed. Further study will be required to define the mechanism of action and to determine whether these vaccine targets will be useful components of an anti-tick vaccine cocktail.

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          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13071-022-05166-1.

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          Most cited references40

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          Perspectives on Immunoglobulins in Colostrum and Milk

          Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.
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            Overview: Ticks as vectors of pathogens that cause disease in humans and animals.

            Ticks (Acari: Ixodidae) transmit a wide variety of pathogens to vertebrates including viruses, bacteria, protozoa and helminthes. Tick-borne pathogens are believed to be responsible for more than 100,000 cases of illness in humans throughout the world. Ticks are considered to be second worldwide to mosquitoes as vectors of human diseases, but they are the most important vectors of disease-causing pathogens in domestic and wild animals. Infection and development of pathogens in both tick and vertebrate hosts are mediated by molecular mechanisms at the tick-pathogen interface. These mechanisms, involving traits of both ticks and pathogens, include the evolution of common and species-specific characteristics. The molecular characterization of the tick-pathogen interface is rapidly advancing and providing new avenues for the development of novel control strategies for both tick infestations and their associated pathogens.
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              A ten-year review of commercial vaccine performance for control of tick infestations on cattle.

              Ticks are important ectoparasites of domestic and wild animals, and tick infestations economically impact cattle production worldwide. Control of cattle tick infestations has been primarily by application of acaricides which has resulted in selection of resistant ticks and environmental pollution. Herein we discuss data from tick vaccine application in Australia, Cuba, Mexico and other Latin American countries. Commercial tick vaccines for cattle based on the Boophilus microplus Bm86 gut antigen have proven to be a feasible tick control method that offers a cost-effective, environmentally friendly alternative to the use of acaricides. Commercial tick vaccines reduced tick infestations on cattle and the intensity of acaricide usage, as well as increasing animal production and reducing transmission of some tick-borne pathogens. Although commercialization of tick vaccines has been difficult owing to previous constraints of antigen discovery, the expense of testing vaccines in cattle, and company restructuring, the success of these vaccines over the past decade has clearly demonstrated their potential as an improved method of tick control for cattle. Development of improved vaccines in the future will be greatly enhanced by new and efficient molecular technologies for antigen discovery and the urgent need for a tick control method to reduce or replace the use of acaricides, especially in regions where extensive tick resistance has occurred.
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                Author and article information

                Contributors
                glen.scoles@usda.gov
                hala.elsayed@wsu.edu
                colds@ksu.edu
                kathleen.mason@usda.gov
                sara.davis@usda.gov
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                8 February 2022
                8 February 2022
                2022
                : 15
                : 49
                Affiliations
                [1 ]GRID grid.30064.31, ISNI 0000 0001 2157 6568, USDA-ARS, Animal Disease Research Unit, Washington State University, ; Pullman, WA USA
                [2 ]GRID grid.30064.31, ISNI 0000 0001 2157 6568, Department of Veterinary Microbiology and Pathology, , Washington State University, ; Pullman, WA USA
                [3 ]GRID grid.7776.1, ISNI 0000 0004 0639 9286, Department of Entomology, Faculty of Science, , Cairo University, ; Giza, Egypt
                [4 ]GRID grid.266456.5, ISNI 0000 0001 2284 9900, Department of Entomology, Plant Pathology and Nematology, , University of Idaho, ; Moscow, ID USA
                [5 ]GRID grid.507312.2, ISNI 0000 0004 0617 0991, Present Address: USDA-ARS, Invasive Insect Biocontrol and Behavior Lab, , Beltsville Agricultural Research Center, ; Beltsville, MD USA
                [6 ]GRID grid.36567.31, ISNI 0000 0001 0737 1259, Present Address: Department of Entomology, , Kansas State University, ; Manhattan, KS USA
                Author information
                http://orcid.org/0000-0003-4161-0756
                Article
                5166
                10.1186/s13071-022-05166-1
                8822678
                1dad23a2-adff-4315-8702-96dc2f495992
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 28 September 2021
                : 17 January 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100007917, Agricultural Research Service;
                Award ID: CRIS project # 2090-32000-039-000-D
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Parasitology
                aquaporin,cattle tick,bm86,igg isotype,anti-tick vaccine
                Parasitology
                aquaporin, cattle tick, bm86, igg isotype, anti-tick vaccine

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