The glycosylphosphatidylinositol-anchored protein repertoire of Babesia bovis and its significance for erythrocyte invasion

Rodríguez, Anabel Elisa; Florín-Christensen, Mónica; Flores, Daniela; Echaide, Ignacio; Suárez, Carlos E.; Schnittger, Leonhard

doi:10.1016/j.ttbdis.2013.12.011

Cited by 29 publications

(24 citation statements)

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“…Recently, the GPI-anchored proteome of B. bovis was predicted using a similar in silico analysis and was shown to be organized in three gene families. 62 Based on the findings of this study, we believe that an optimal diagnostic assay for B. microti should include BmGPI12 as a bait to detect anti-BmGPI12 antibodies or as an antigen target in a direct detection assay using high-affinity anti-BmGPI12 antibody or a combination of both. Interestingly, this protein is unique to B. microti and available data suggest that it undergoes little to no variation between different isolates.…”

Section: Discussionmentioning

confidence: 80%

“…In Toxoplasma , specific antigens such as SAG and BSR are expressed at different stages of development, whereas in Plasmodium , about half of the predicted GPI‐anchored proteins are transcribed during blood stage development. Recently, the GPI‐anchored proteome of B. bovis was predicted using a similar in silico analysis and was shown to be organized in three gene families …”

Section: Discussionmentioning

confidence: 99%

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A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

et al. 2016

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BACKGROUND Babesia microti is a protozoan parasite responsible for the majority of reported cases of human babesiosis and a major risk to the blood supply. Laboratory screening of blood donors may help prevent transfusion-transmitted babesiosis but there is no Food and Drug Administration–approved screening method yet available. Development of a sensitive, specific, and highly automated B. microti antibody assay for diagnosis of acute babesiosis and blood screening could have an important impact on decreasing the health burden of B. microti infection. STUDY DESIGN AND METHODS Herein, we take advantage of recent advances in B. microti genomic analyses, field surveys of the reservoir host, and human studies in endemic areas to apply a targeted immunomic approach to the discovery of B. microti antigens that serve as signatures of active or past babesiosis infections. Of 19 glycosylphosphatidylinositol (GPI)-anchored protein candidates (BmGPI1-19) identified in the B. microti proteome, 17 were successfully expressed, printed on a microarray chip, and used to screen sera from uninfected and B. microti–infected mice and humans to determine immune responses that are associated with active and past infection. RESULTS Antibody responses to various B. microti BmGPI antigens were detected and BmGPI12 was identified as the best biomarker of infection that provided high sensitivity and specificity when used in a microarray antibody assay. CONCLUSION BmGPI12 alone or in combination with other BmGPI proteins is a promising candidate biomarker for detection of B. microti antibodies that might be useful in blood screening to prevent transfusion-transmitted babesiosis.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

et al. 2016

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“…Additionally, inhibition of GPI synthesis prevents in vitro growth of parasites in erythrocytes, corroborating the importance of these antigens in the process of invasion [15]. Furthermore, the release of GPI-anchored proteins from parasite cell membranes via treatment with phosphatidylinositol-specific phospholipase C prevents erythrocyte invasion by B. bovis merozoites [16]. As invasion of red blood cells is crucial to the survival of the parasite, blocking the antigens involved in this process may lead to protection.…”

Section: Introductionmentioning

confidence: 89%

“…Babesia bovis merozoites of the Argentine S2P pathogenic strain (BboS2P) were cultured in vitro on bovine erythrocytes, as described previously [16]. Growth was monitored by microscopic observation of Giemsa-stained smears.…”

Section: Methodsmentioning

confidence: 99%

A recombinant multi-antigen vaccine formulation containing Babesia bovis merozoite surface antigens MSA-2a1, MSA-2b and MSA-2c elicits invasion-inhibitory antibodies and IFN-γ producing cells

et al. 2016

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Background Babesia bovis is a tick-transmitted protozoan hemoparasite and the causative agent of bovine babesiosis, a potential risk to more than 500 million cattle worldwide. The vaccines currently available are based on attenuated parasites, which are difficult to produce, and are only recommended for use in bovines under one year of age. When used in older animals, these vaccines may cause life-threatening clinical symptoms and eventually death. The development of a multi-subunit recombinant vaccine against B. bovis would be attractive from an economic standpoint and, most importantly, could be recommended for animals of any age. In the present study, recombinant ectodomains of MSA-2a1, MSA-2b and MSA-2c antigens were expressed in Pichia pastoris yeast as secreted soluble peptides.ResultsThe antigens were purified to homogeneity, and biochemically and immunologically characterized. A vaccine formulation was obtained by emulsifying a mixture of the three peptides with the adjuvant Montanide ISA 720, which elicited high IgG antibody titers against each of the above antigens. IgG antibodies generated against each MSA-antigen recognized merozoites and significantly inhibited the invasion of bovine erythrocytes. Cellular immune responses were also detected, which were characterized by splenic and lymph node CD4+ T cells producing IFN-γ and TNF-α upon stimulation with the antigens MSA-2a1 or MSA-2c.ConclusionsThese data strongly suggest the high protective potential of the presented formulation, and we propose that it could be tested in vaccination trials of bovines challenged with B. bovis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1862-1) contains supplementary material, which is available to authorized users.

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“…Notably, the R. microplus 5′ nucleotidase (listed as a 'secreted protein') was predicted to have a 'weakly probable GPI anchor' , and it is known that mammalian 5′ nucleotidases possess GPI anchors [10]. In terms of vaccine candidates, GPI-anchored proteins have been investigated in several parasite species such as Leishmania amazonensis [44], Plasmodium falciparum [45], Schistosoma mansoni [46], Theileria annulata [47] and Babesia bovis [48] and have appeared to be associated with host invasion. In mammals, certain GPI-anchored proteins are cytokines with complement regulation functions [10].…”

Section: Membrane-bound Antigensmentioning

confidence: 99%

The Enigma of Identifying New Cattle Tick Vaccine Antigens

Lew-Tabor¹

2019

Ticks and Tick-Borne Pathogens

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Several reviews have summarised cattle tick Rhipicephalus (Boophilus) microplus vaccine candidate discoveries by comparing efficacies and localisation characteristics. However, few have re-analysed all the reported proteins using modern bioinformatics tools. Bm86 was developed as a successful vaccine in the 1980s; however, global efficacies vary from 45 to 100%. Subsequent vaccines, including four published patents, were discovered by targeting enzymes important for blood digestion and/or metabolism or by targeting genes shown to disrupt tick survival following RNA interference experiments. This chapter analyses published vaccine candidates using InterPro, BLASTP, SignalP, TMHMM and PredGPI tools to confirm whether each reported protein is likely to be secreted, membrane associated or intracellular. Conversely, these proteins are considered as 'exposed' , 'exposed' and 'concealed' or 'concealed' , respectively. Bm86 was always described as a 'concealed' antigen; however, the protein has a confirmed signal peptide and GPI anchor which suggests it is anchored to the cell membrane and exposed on the surface of gut cells. It is the only tick vaccine with a GPI anchor. Secreted vaccine candidates appear to have promise and exhibit higher efficacies if delivered with an 'intracellular'/'concealed' antigen. Improvements in tick genomics and bovine immunomic resources will assist to identify robust new cattle tick vaccines.

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The glycosylphosphatidylinositol-anchored protein repertoire of Babesia bovis and its significance for erythrocyte invasion

Cited by 29 publications

References 54 publications

A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

A recombinant multi-antigen vaccine formulation containing Babesia bovis merozoite surface antigens MSA-2a1, MSA-2b and MSA-2c elicits invasion-inhibitory antibodies and IFN-γ producing cells

The Enigma of Identifying New Cattle Tick Vaccine Antigens

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