Vaccination against babesiosis using recombinant GPI-anchored proteins

Wieser, Sarah N.; Schnittger, Leonhard; Florín-Christensen, Mónica; Delbecq, Stéphane; Schetters, Theo

doi:10.1016/j.ijpara.2018.12.002

Cited by 27 publications

(18 citation statements)

References 34 publications

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“…Interestingly, one of the intriguing features of parasite GPIs is that they could be released or shed from the cell surface of parasites. It has been reported that when parasites invade erythrocyte, the merozoite surface coat will be shed or left outside the erythrocyte (Nathaly Wieser et al, 2019) and the secreted proteins were soluble and different from those on the surface coat of merozoites (Casanova et al, 2006). These reported features are not completely in 2 http://www.cbs.dtu.dk/services/SignalP-4.1 agreement with the findings in the present study.…”

Section: Discussionsupporting

confidence: 77%

“…In this process, Babesia will secrete antigens which can help parasites effectively recognize and adhere to host RBCs, then the parasite will form the tight junction between erythrocyte surface and apical part and start invasion (Yokoyama et al, 2006). Due to their direct exposure to the host's immune system, these antigens are also very effective in stimulating the host's immune system, causing a host of immune responses, including the humoral and cellular immune responses (Nathaly Wieser et al, 2019). For this reason, the secreted antigen has become a vaccine candidate in developing the Babesia vaccine, and it may also facilitate the development of a diagnostic test for babesiosis.…”

Section: Introductionmentioning

confidence: 99%

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Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

Guo

et al. 2020

Front. Microbiol.

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Babesia microti, a tick-borne intraerythrocytic zoonotic protozoan, causes most of human babesiosis in the world, and patients usually experience intermittent fever, fatigue, and chills, followed by a combination of additional symptoms and even death in severe cases. Unfortunately, there is no curable drug or effective vaccine available, and the mechanism of related virulence factors in invasion to host cells during the merozoite stage is unclear. Here, we evaluated a secreted protein annotated as B. microti surface antigen 1 (BmSA1) and identified from in vitro culture supernatant by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). BmSA1 fragment was expressed in Escherichia coli to prepare polyclonal antiserum. Western blot analysis revealed the existence of BmSA1 in the lysate of the parasites and the hemolysate of infected red blood cells (iRBCs). Laser confocal microscopy confirmed BmSA1 as a secreted protein with diffuse distribution around the parasites in red blood cells (RBCs). The adhesion capacity of BmSA1 against the host RBCs was tested by RBC binding assays using the recombinant BmSA1 protein (rBmSA1), which was shown to specifically bind to host RBCs. Further in vitro antiserum-neutralization test demonstrated that the growth of parasites could be significantly inhibited by the anti-BmSA1 antiserum. These results indicate that BmSA1 is a crucial factor for B. microti invasion into host RBCs with an important role in host-parasite interactions during the merozoite stage and has the potential use as a vaccine candidate due to its high secretion amount.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

Guo

et al. 2020

Front. Microbiol.

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“…deer clade, sometimes referred to as the European variant of Babesia odocoilei [7]. Particularly Babesia species from clade X are of economic importance in the livestock industry [8,9]. In addition, both clades comprise some species that are considered zoonotic and can affect human health [10,11].…”

Section: Introductionmentioning

confidence: 99%

Circulation of Babesia Species and Their Exposure to Humans through Ixodes ricinus

et al. 2021

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Human babesiosis in Europe has been attributed to infection with Babesia divergens and, to a lesser extent, with Babesia venatorum and Babesia microti, which are all transmitted to humans through a bite of Ixodes ricinus. These Babesia species circulate in the Netherlands, but autochthonous human babesiosis cases have not been reported so far. To gain more insight into the natural sources of these Babesia species, their presence in reservoir hosts and in I. ricinus was examined. Moreover, part of the ticks were tested for co-infections with other tick borne pathogens. In a cross-sectional study, qPCR-detection was used to determine the presence of Babesia species in 4611 tissue samples from 27 mammalian species and 13 bird species. Reverse line blotting (RLB) and qPCR detection of Babesia species were used to test 25,849 questing I. ricinus. Fragments of the 18S rDNA and cytochrome c oxidase subunit I (COI) gene from PCR-positive isolates were sequenced for confirmation and species identification and species-specific PCR reactions were performed on samples with suspected mixed infections. Babesia microti was found in two widespread rodent species: Myodes glareolus and Apodemus sylvaticus, whereas B. divergens was detected in the geographically restricted Cervus elaphus and Bison bonasus, and occasionally in free-ranging Ovis aries. B. venatorum was detected in the ubiquitous Capreolus capreolus, and occasionally in free-ranging O. aries. Species-specific PCR revealed co-infections in C. capreolus and C. elaphus, resulting in higher prevalence of B. venatorum and B. divergens than disclosed by qPCR detection, followed by 18S rDNA and COI sequencing. The non-zoonotic Babesia species found were Babesia capreoli, Babesia vulpes, Babesia sp. deer clade, and badger-associated Babesia species. The infection rate of zoonotic Babesia species in questing I. ricinus ticks was higher for Babesia clade I (2.6%) than Babesia clade X (1.9%). Co-infection of B. microti with Borrelia burgdorferi sensu lato and Neoehrlichia mikurensis in questing nymphs occurred more than expected, which reflects their mutual reservoir hosts, and suggests the possibility of co-transmission of these three pathogens to humans during a tick bite. The ubiquitous spread and abundance of B. microti and B. venatorum in their reservoir hosts and questing ticks imply some level of human exposure through tick bites. The restricted distribution of the wild reservoir hosts for B. divergens and its low infection rate in ticks might contribute to the absence of reported autochthonous cases of human babesiosis in the Netherlands.

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“…In recent years, several proteins involved in cell invasion and immunity have been developed as vaccine candidates and their protections against Babesia infection in animal models have been evaluated ( 8 – 13 ). But all these candidates as vaccines exhibited limited protection from the infection of Babesia .…”

Section: Introductionmentioning

confidence: 99%

Babesia microti Protein BmSP44 Is a Novel Protective Antigen in a Mouse Model of Babesiosis

Wang

Huang

et al. 2020

Front. Immunol.

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Babesiosis caused by Babesia species imposes an increasing threat to public-health and so far, there is no effective vaccine to prevent Babesia infections. Babesia surface antigen may participate in the invasion of erythrocytes. In our previous study, a surface antigen of B. microti merozoites, named as Bm SP44 was identified as a dominant reactive antigen by protein microarray screening. To evaluate its potential applications in diagnosis and prevention of Babesiosis, the open reading frame encoding Bm SP44 was cloned and the recombinant protein was expressed. In consistent with the protein microarray result, recombinant Bm SP44 (r Bm SP44) can be recognized by sera from B. microti infected mice. Immunofluorescence assays (IFA) confirmed that Bm SP44 is a secreted protein and localized principally in the cytoplasm of the parasites. The parasitemia and Babesia gene copies were lower in mice administered r Bm SP44 antisera compared with normal controls. Active immunization with r Bm SP44 also afforded protection against B. microti infection. The concentrations of hemoglobin in r Bm SP44 immunization group were higher than those in the control group. Importantly, vaccination of mice with r Bm SP44 resulted in a Th1/Th2 mixed immune response with significantly elevated IL-10 and IFN-γ levels during the early stage of infection. Taken together, our results indicated that r Bm SP44 can induce a protective immune response against Babesia infection. Thus, Bm SP44 can be used as both a diagnosis marker and a vaccine candidate.

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Vaccination against babesiosis using recombinant GPI-anchored proteins

Cited by 27 publications

References 34 publications

Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

Circulation of Babesia Species and Their Exposure to Humans through Ixodes ricinus

Babesia microti Protein BmSP44 Is a Novel Protective Antigen in a Mouse Model of Babesiosis

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