A Babesia bovis gene syntenic to Theileria parva p67 is expressed in blood and tick stage parasites

Freeman, Jeanne M.; Kappmeyer, Lowell S.; Ueti, Massaro W.; McElwain, Terry F.; Baszler, Timothy V.; Echaide, Ignacio; Nene, Vishvanath; Knowles, Donald P.

doi:10.1016/j.vetpar.2010.06.024

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…We searched for C. felis orthologues of p67 and SPAG-1 but found no sequences with significant amino acid similarity. Therefore, guided by the approach used to identify the p67/SPAG-1 orthologue in Babesia bovis (BOV57), we used conserved genome synteny to expose the C. felis orthologue of p67/SPAG-1, which we call cf76 [24]. Here we report our assessment of three criteria likely to be important in determining suitability of cf76 as a vaccine candidate: 1) recognition by the feline immune system 2) degree of sequence similarity among C. felis isolates and 3) expression in the C. felis life stage that is believed to be critical for the development of a protective immune response.…”

Section: Introductionmentioning

confidence: 99%

A Novel Candidate Vaccine for Cytauxzoonosis Inferred from Comparative Apicomplexan Genomics

et al. 2013

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Cytauxzoonosis is an emerging infectious disease of domestic cats (Felis catus) caused by the apicomplexan protozoan parasite Cytauxzoon felis. The growing epidemic, with its high morbidity and mortality points to the need for a protective vaccine against cytauxzoonosis. Unfortunately, the causative agent has yet to be cultured continuously in vitro, rendering traditional vaccine development approaches beyond reach. Here we report the use of comparative genomics to computationally and experimentally interpret the C. felis genome to identify a novel candidate vaccine antigen for cytauxzoonosis. As a starting point we sequenced, assembled, and annotated the C. felis genome and the proteins it encodes. Whole genome alignment revealed considerable conserved synteny with other apicomplexans. In particular, alignments with the bovine parasite Theileria parva revealed that a C. felis gene, cf76, is syntenic to p67 (the leading vaccine candidate for bovine theileriosis), despite a lack of significant sequence similarity. Recombinant subdomains of cf76 were challenged with survivor-cat antiserum and found to be highly seroreactive. Comparison of eleven geographically diverse samples from the south-central and southeastern USA demonstrated 91–100% amino acid sequence identity across cf76, including a high level of conservation in an immunogenic 226 amino acid (24 kDa) carboxyl terminal domain. Using in situ hybridization, transcription of cf76 was documented in the schizogenous stage of parasite replication, the life stage that is believed to be the most important for development of a protective immune response. Collectively, these data point to identification of the first potential vaccine candidate antigen for cytauxzoonosis. Further, our bioinformatic approach emphasizes the use of comparative genomics as an accelerated path to developing vaccines against experimentally intractable pathogens.

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Section: Introductionmentioning

confidence: 99%

A Novel Candidate Vaccine for Cytauxzoonosis Inferred from Comparative Apicomplexan Genomics

et al. 2013

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“…A positional homolog was identified in B . bovis (BBOV_IV007750) [29,59] and T . equi contains a gene at the same location (BEWA_015160).…”

Section: Resultsmentioning

confidence: 99%

Comparative genomic analysis and phylogenetic position of Theileria equi

et al. 2012

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BackgroundTransmission of arthropod-borne apicomplexan parasites that cause disease and result in death or persistent infection represents a major challenge to global human and animal health. First described in 1901 as Piroplasma equi, this re-emergent apicomplexan parasite was renamed Babesia equi and subsequently Theileria equi, reflecting an uncertain taxonomy. Understanding mechanisms by which apicomplexan parasites evade immune or chemotherapeutic elimination is required for development of effective vaccines or chemotherapeutics. The continued risk of transmission of T. equi from clinically silent, persistently infected equids impedes the goal of returning the U. S. to non-endemic status. Therefore comparative genomic analysis of T. equi was undertaken to: 1) identify genes contributing to immune evasion and persistence in equid hosts, 2) identify genes involved in PBMC infection biology and 3) define the phylogenetic position of T. equi relative to sequenced apicomplexan parasites.ResultsThe known immunodominant proteins, EMA1, 2 and 3 were discovered to belong to a ten member gene family with a mean amino acid identity, in pairwise comparisons, of 39%. Importantly, the amino acid diversity of EMAs is distributed throughout the length of the proteins. Eight of the EMA genes were simultaneously transcribed. As the agents that cause bovine theileriosis infect and transform host cell PBMCs, we confirmed that T. equi infects equine PBMCs, however, there is no evidence of host cell transformation. Indeed, a number of genes identified as potential manipulators of the host cell phenotype are absent from the T. equi genome. Comparative genomic analysis of T. equi revealed the phylogenetic positioning relative to seven apicomplexan parasites using deduced amino acid sequences from 150 genes placed it as a sister taxon to Theileria spp.ConclusionsThe EMA family does not fit the paradigm for classical antigenic variation, and we propose a novel model describing the role of the EMA family in persistence. T. equi has lost the putative genes for host cell transformation, or the genes were acquired by T. parva and T. annulata after divergence from T. equi. Our analysis identified 50 genes that will be useful for definitive phylogenetic classification of T. equi and closely related organisms.

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“…In B. bovis , RAP-1, MSA-1, MSA-2a, 2b and 2c are expressed in sporozoites (Mosqueda et al 2002 a , b ). In addition, a protein with similarities with p67, a Theileria parva partially protective antigen against East coast fever, was shown to be expressed in kinetes, as well as in intra-erythrocytic forms (Freeman et al 2010).…”

Section: Puzzle Pieces For Novel Vaccinesmentioning

confidence: 99%

Vaccines against bovine babesiosis: where we are now and possible roads ahead

Florín-Christensen

Suárez

Rodríguez³

et al. 2014

Parasitology

106

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SUMMARY Bovine babesiosis caused by the tick-transmitted haemoprotozoans Babesia bovis, Babesia bigemina and Babesia divergens commonly results in substantial cattle morbidity and mortality in vast world areas. Although existing live vaccines confer protection, they have considerable disadvantages. Therefore, particularly in countries where large numbers of cattle are at risk, important research is directed towards improved vaccination strategies. Here a comprehensive overview of currently used live vaccines and of the status quo of experimental vaccine trials is presented. In addition, pertinent research fields potentially contributing to the development of novel non-live and/or live vaccines are discussed, including parasite antigens involved in host cell invasion and in pathogen-tick interactions, as well as the protective immunity against infection. The mining of available parasite genomes is continuously enlarging the array of potential vaccine candidates and, additionally, the recent development of a transfection tool for Babesia can significantly contribute to vaccine design. However, the complication and high cost of vaccination trials hinder Babesia vaccine research, and have so far seriously limited the systematic examination of antigen candidates and prevented an in-depth testing of formulations using different immunomodulators and antigen delivery systems.

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A Babesia bovis gene syntenic to Theileria parva p67 is expressed in blood and tick stage parasites

Cited by 10 publications

References 21 publications

A Novel Candidate Vaccine for Cytauxzoonosis Inferred from Comparative Apicomplexan Genomics

A Novel Candidate Vaccine for Cytauxzoonosis Inferred from Comparative Apicomplexan Genomics

Comparative genomic analysis and phylogenetic position of Theileria equi

Vaccines against bovine babesiosis: where we are now and possible roads ahead

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