anti-tick vaccines to prevent tick-borne diseases in Europe

Ixodes ricinus transmits bacterial, protozoal and viral pathogens, causing disease and forming an increasing health concern in Europe. ANTIDotE is an European Commission funded consortium of seven institutes, which aims to identify and characterize tick proteins involved in feeding and pathogen transmission. The knowledge gained will be used to develop and evaluate anti- tick vaccines that may prevent multiple human tick-borne diseases. Strategies encompassing anti-tick vaccines to prevent transmission of pathogens to humans, animals or wildlife will be developed with relevant stakeholders with the ultimate aim of reducing the incidence of tick-borne diseases in humans

Mechanisms involved in the persistence of Babesia canis infection in dogs

Dogs that are infected with Babesia canis parasites usually show severe clinical signs, yet often very few parasites are detectable in the blood circulation. The results showed that large numbers of B. canis-infected red blood cells accumulate in the microvasculature of infected subjects. The initial process leading to the attachment of infected erythrocytes to the endothelial cells of small capillaries (sequestration) appears to involve the interaction of parasite molecules at the erythrocyte surface with ligands on the endothelial cells. Since parasites continue to develop in the sequestered erythrocyte, it would be expected that the infected erythrocyte is destroyed when the mature parasites escape the host cell, which would make it hard to explain accumulation of infected erythrocytes at the initial site of attachment. Apparently, additional processes are triggered that lead to consolidation of parasite sequestration. One possible explanation is that after initial attachment of an infected erythrocyte to the wall of a blood capillary, the coagulation system is involved in the trapping of infected and uninfected erythrocytes. The data further suggest that newly formed parasites subsequently infect normal red blood cells that are also trapped in the capillary, which finally leads to capillaries that appear to be loaded with infected erythrocytes.https://www.mdpi.com/journal/pathogenshj2020Veterinary Tropical Disease

First molecular diagnosis of Babesia vogeli in domestic dogs from Turkey

Microscopic examination of Giemsa-stained peripheral blood smears collected from three naturally infected dogs originating from Turkey revealed the presence of large (around 4.5-5.0 mu m) intraerythrocytic Babesia parasites in all dogs. DNA was extracted from the three infected blood samples and an around 410 bp portion of the 18 S rDNA gene of Babesia species was PCR amplified for subsequent molecular characterization. RFLP analysis of the PCR products suggested the presence of the species B. vogeli in all infected dogs and sequencing of the PCR products from two of the three samples revealed 100% identity among the two Turkish isolates. Comparisons with the equivalent 4 10 bp portions of the 18 S rDNA gene of Babesia species confirmed the affiliation of these isolates to the B. vogeli species. This is the first report and molecular characterization of dog infection with a large Babesia species in Turkey. (c) 2006 Elsevier B.V. All rights reserved

Vaccination against babesiosis using recombinant GPI-anchored proteins

In Press, Corrected ProofThe increase in human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe B. divergens is the major cause of clinical disease in humans. Here we review the immunological and biological literature of glycosylphosphatidylinositol (GPI)-anchored merozoite proteins of human Babesia parasites with emphasis on their role in immunity, and provide some new bioinformatical information on B. microti GPI-Anchored Proteins (GPI-AP). Cattle can be vaccinated with soluble parasite antigens (SPA) of Babesia divergens that are released by the parasite during proliferation. The major component in SPA preparations appeared to be a 37 kDa merozoite surface protein that is anchored in the merozoite membrane by a GPI anchor. Animals could be protected by vaccination with the recombinant 37 kDa protein expressed in Escherichia coli, provided the protein had a hydrophobic terminal sequence. Based on this knowledge, a recombinant vaccine was developed against Babesia canis infection in dogs, successfully. In order to identify similar GPI-AP in B. microti, the genome was analysed. Here it is shown that B. microti encodes all proteins necessary for GPI assembly and its subsequent protein transfer. In addition, in total 21 genes encoding for GPI-AP were detected, some of which reacted particularly strongly with sera from B. microti-infected human patients. Reactivity of antibodies with GPI-anchored merozoite proteins appears to be dependent on the structural conformation of the molecule. It is suggested that the three-dimensional structure of the protein that is anchored in the membrane is different from that of the protein that has been shed from the merozoite surface. The significance of this protein’s dynamics in parasite biology and immune evasion is discussed. Finally, we discuss developments in tick and Babesia vaccine research, and the role such vaccines could play in the control of human babesiosis.Instituto de PatobiologíaFil: Wieser, Sarah Nathaly. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Florin-Christensen, Monica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Delbecq, Stephane. Université de Montpellier.· Vaccination Antiparasitaire; FranciaFil: Schetters, Theo. Université de Montpellier.· Vaccination Antiparasitaire; Francia. University of Pretoria. Veterinary Faculty. Department of Veterinary Tropical Diseases; Sudáfric

Structural and Functional Characterization of Bc28.1, Major Erythrocyte-binding Protein from Babesia canis Merozoite Surface

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The solution structure of the adhesion protein Bd37 from Babesia divergens reveals structural homology with eukaryotic proteins involved in membrane trafficking.

Babesia divergens is the Apicomplexa agent of the bovine babesiosis in Europe: this infection leads to growth and lactation decrease, so that economical losses due to this parasite are sufficient to require the development of a vaccine. The major surface antigen of B. divergens has been described as a 37 kDa protein glycosyl phosphatidyl inositol (GPI)-anchored at the surface of the merozoite. The immuno-prophylactic potential of Bd37 has been demonstrated, and we present here the high-resolution solution structure of the 27 kDa structured core of Bd37 (Delta-Bd37) using NMR spectroscopy. A model for the whole protein has been obtained using additional small angle X-ray scattering (SAXS) data. The knowledge of the 3D structure of Bd37 allowed the precise epitope mapping of antibodies on its surface. Interestingly, the geometry of Delta-Bd37 reveals an intriguing similarity with the exocyst subunit Exo84p C-terminal region, an eukaryotic protein that has a direct implication in vesicle trafficking. This strongly suggests that Apicomplexa have developed in parallel molecular machines similar in structure and function to the ones used for endo- and exocytosis in eukaryotic cells

Biology

The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas

A combination of antibodies against Bm86 and Subolesin inhibits engorgement of Rhipicephalus australis (formerly Rhipicephalus microplus) larvae in vitro

Background: Rhipicephalus microplus is a hard tick species that has a high impact on cattle health and production in tropical and subtropical regions. Recently, ribosomal DNA and morphological analysis resulted in the reinstatement of R. australis as a separate species from R. microplus. Both feed on cattle and can transmit bovine pathogens such as Anaplasma and Babesia species. The current treatment with acaricides is becoming increasingly less effective due to the emergence of resistant tick strains. A promising alternative can be found in the form of anti-tick vaccines. The available commercial vaccines can be used to control tick infestation, but the lack of a knockdown effect (> 90% reduction in tick numbers as seen with effective acaricides) hampers its widespread use, hence higher efficacious vaccines are needed. Instead of searching for new protective antigens, we investigated the efficacy of vaccines that contain more than one (partially) protective antigen. For screening vaccine formulations, a previously developed in vitro feeding assay was used in which R. australis larvae are fed sera that were raised against the candidate vaccine antigens. In the present study, the efficacy of the Bm86 midgut antigen and the cytosolic Subolesin (SUB) antigen were evaluated in vitro. Results: Antiserum against recombinant Bm86 (rBm86) partially inhibited larval engorgement, whereas antiserum against recombinant SUB (rSUB) did not have any effect on feeding of larvae. Importantly, when larvae were fed a combination of antiserum against rBm86 and rSUB, a synergistic effect on significantly reducing larval infestations was found. Immunohistochemical analysis revealed that the rBm86 antiserum reacted with gut epithelium of R. australis larvae, whereas the antiserum against rSUB stained salivary glands and rectal sac epithelium. Conclusions: Combining anti-Bm86 and anti-subolesin antibodies synergistically reduced R. australis larval feeding in vitro. Rhipicephalus australis is a one host tick, meaning that the larvae develop to nymphs and subsequently adults on the same host. Hence, this protective effect could be even more pronounced when larvae are used for infestation of vaccinated cattle, as the antibodies could then affect all three developmental stages. This will be tested in future in vivo experiments

Invasive cattle ticks in East Africa : morphological and molecular confirmation of the presence of Rhipicephalus microplus in south‑eastern Uganda

BACKGROUND : Rhipicephalus microplus, an invasive tick species of Asian origin and the main vector of Babesia species, is considered one of the most widespread ectoparasites of livestock. The tick has spread from its native habitats on translocated livestock to large parts of the tropical world, where it has replaced some of the local populations of Rhipicephalus decoloratus ticks. Although the tick was reported in Uganda 70 years ago, it has not been found in any subsequent surveys. This study was carried out to update the national tick species distribution on livestock in Uganda as a basis for tick and tick-borne disease control, with particular reference to R. microplus. METHODS : The study was carried out in Kadungulu, Serere district, south-eastern Uganda, which is dominated by small scale livestock producers. All the ticks collected from 240 cattle from six villages were identified microscopically. Five R. microplus specimens were further processed for phylogenetic analysis and species confirmation. RESULTS : The predominant tick species found on cattle was Rhipicephalus appendiculatus (86.9 %; n = 16,509). Other species found were Amblyomma variegatum (7.2 %; n = 1377), Rhipicephalus evertsi (2.3 %; n = 434) and R. microplus (3.6 %; n = 687). Phylogenetic analysis of the 12S rRNA, 16S rRNA and ITS2 gene sequences of R. microplus confirmed the morphological identification. CONCLUSIONS : It is concluded that R. microplus has replaced R. decoloratus in the sampled villages in Kadungulu subcounty, since the latter was not any longer found in this area. There is currently no livestock movement policy in force in Uganda, which could possibly limit the further spread of R. microplus ticks. Future surveys, but also retrospective surveys of museum specimens, will reveal the extent of distribution of R. microplus in Uganda and also for how long this tick has been present on livestock without being noticed.The Bill & Melinda Gates Foundation (BMGF) through ClinVet International (Pty), the Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII), the DELTAS Africa Initiative, the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa’s Development Planning and Coordinating Agency, the Wellcome Trust and the UK government.http://www.parasitesandvectors.comam2021Veterinary Tropical Disease