VIOLIN: Vaccine Investigation and Online Information Network

Theileria annulata

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. sp (Protective antigen)
2. spag-1 (Protective antigen)
3. TA17050 merozoite-piroplasm surface antigen Tams1 (Protective antigen)
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

5874

2. Disease:

Theileriosis

3. Introduction

Tropical theileriosis or Mediterranean theileriosis is a theileriosis of cattle from the Mediterranean and Middle East area, from Morocco to Western parts of India and China. It is a tick-borne disease, caused by Theileria annulata. The vector ticks are of the genus Hyalomma. The most prominent symptoms are fever and lymph node enlargement. But there is a wide range of clinical manifestations, especially in enzootic areas. Among them, the Doukkala area of Morocco, where the epidemiology and symptomatology of the disease were minutely studied (Wiki: T. annulata).

4. Microbial Pathogenesis

Three stages in the life cycle of the parasite--tick-derived sporozoites, intramononuclear schizonts, and erythrocytic merozoites--infect cattle. When cattle are inoculated with schizont-infected cells, the parasite is transferred from the donor cell to the recipient. The main pathological damage in cattle is induced by the schizont stage. Each development stage of T. annulata elicits a specific immune response. Schizont-infected lymphoid cells can be grown indefinitely in culture and prolonged cultivation results in loss of virulence. Blood-derived schizonts induce stronger immunity than culture-derived schizonts, which suggests that restrictions on the parasite population or antigenic variation occur during prolonged cultivation. The duration of immunity following sporozoite or schizont infections has not yet been determined, but does not appear to be lifelong (Pipano and Shkap, 2000).

5. Host Ranges and Animal Models

Tropical theileriosis is maintained in nature by a cattle-tick-cattle cycle, both taurine (Bos taurus) and zebu (Bos indicus) cattle being susceptible to the disease. The yak (Bos grunniens) is also highly susceptible and suffers severe clinical symptoms and mortality following infection with T. annulata. The water buffalo (Bubalus bubalis) does not usually exhibit clinical manifestation on infection, but may act as a reservoir for the infection of ticks (Pipano and Shkap, 2000).

6. Host Protective Immunity

Each of the three developmental stages of T. annulata that are infective for cattle (sporozoites, schizonts, and erythrocytic merozoites) induces a specific immune response that may result in partial or no protection against infection with the heterologous stages (Pipano and Shkap, 2000).

II. Vaccine Related Pathogen Genes

1. sp

Gene Name : sp
Sequence Strain (Species/Organism) : Theileria annulata
NCBI Protein GI : CAC87894
Other Database IDs : CDD:289191
CDD:281302
CDD:292389
CDD:282057
GOA:Q8WPH7
InterPro: IPR007274
InterPro: IPR022131
UniProtKB/TrEMBL: Q8WPH7
Taxonomy ID : 5874
Protein Name : surface protein
Protein pI : 4.39
Protein Weight : 34105.81
Protein Length : 369
Protein Note : Surface protein; pfam12406

Protein Sequence : Show Sequence

>CAC87894.1 surface protein [Theileria annulata]
MKFFYLFVLFPILLKFCECGPFLPLDRQLNPIDFDPNDDQHPLDPDQLIDQIEPSEQPAQQEPIEPQQPT
QPSTEPEELEPETVTVEVPETVTSEEPKESDQTEEQKHEEPEASPAPEPVDEPAVQPTESTPTKASSSGD
AAAPCHGKHHDHDSDGKESKSDHYKPPKDKKPFVPKTSQCCGAFFTNSYKITVAFDWWLCDKPWQYALTL
LALFGFSLLSPCLKAYREVLRAKAIRSFIFDCFLTHLFLFLIAFCAYALDFLLMLVVMTFNVGVFFAVIT
GYTVGYLVSSLAYSTLRSHPARSSSFSRINEDCC

Molecule Role : Protective antigen
Molecule Role Annotation : (Schnittger et al., 2002)

2. spag-1

Gene Name : spag-1
Sequence Strain (Species/Organism) : Theileria annulata
VO ID : VO_0011187
NCBI Protein GI : 161885
Other Database IDs : CDD:253298
Taxonomy ID : 5874
Gene Strand (Orientation) : ?
Protein Name : sporozoite surface antigen
Protein pI : 4.77
Protein Weight : 83569.63
Protein Length : 981
Protein Note : Sporozoite P67 surface antigen; pfam05642

Protein Sequence : Show Sequence

>AAA30134.1 sporozoite surface antigen [Theileria annulata]
MNIIHFLLTIPAIFVSGADKMPAGESSRTSKPSPLVTLESAVTQPSKDPFKTISALSKATKVWKSAVSVS
GDSKTVPTPVSEPMITRSFQEPVSQELEFQSDTEINESGSGSDEDEDDDDDEEEEEDDKSTSSKNGKGSP
KAQPGVSSSSTSSASPTSPTTTLSQTGLGPSGSHAQQDPGVGVPGVGVPGVGVPGVGVPGVGVPGVGVPG
VGGVPGVGVAPGVGVPGVGVAPGVGVGADSSGLPGSGGLGAGAKAGKGQGSGLQGPGGVGVVPGVGVAAS
SSSPGKPPGVGAGVMPGVGVRAQGGVIIGAPGVAGVPGGKPGQPVSQELELKSDTEINESGSSSEGEDDD
DEEEEEENKSTSSKGAGGKAGKGQGSVSPGGGSSASQTSPTTTPQSGLASSGSHAQQSPQQDPAPSKPSG
GGVPGVGVPGVGVPGVGVPGVGVAPGVGVVPGVGGATTSSSSTTSTSTSTTTTTTTSSGKPSDQGSHGTS
PRNAVTRQTDSISGPIPSPGDPRAITGQMGEGERFAVQFLGDFKPKPRRYEGQGTDAVKLKQFIFEEVKS
LVQTLINLKLAIANDFVEISEKLKKKNQNYVPKLKLLKGEQFDTKQKVANVLKGFNSLYFVFFMNLNLAK
EVNKPEELAEFLWKLNTIPDKVGREFELAIEKTKGSEKKKELEEAFNSIGLGFKIAQYATNDILSSITNS
VYSLIKLKNFGDDFVTEVRKSLQMVPHQKNLNGSAFIVKISEIINKKGTEDQDQTSGSGSKGTEGGSLRG
QDLTEEEVLKVLDELVKDVSEEHVGIGDLSDPSSRTPNAKPAELGPSLVIQNVPSDPSKVTPTQPSNLPQ
VPTTGPGNGTDGTTTGPGGNGEGGKDLKEGEKKEGLFQKIKNKLLGSGFEVASIIIPMTTIIFSIVH

Molecule Role : Protective antigen
Molecule Role Annotation : The trial vaccination of cattle against T. annulata using recombinant sporozoite antigens (SPAG-1 and p67) and/or merozoite antigens (TAMS 1-1 and 1-2). The aim of these trials was to try and enhance the levels of protection induced compared with previous trials. Different approaches were tried. SPAG-1 was expressed as a fusion protein with a His6 tag and then either incorporated into ISCOMs, with or without TAMS 1-1 and 1-2, or administered with RWL, a proprietary saponin-based adjuvant. Cross-protection studies were also performed by immunizing cattle with the T. parva sporozoite antigen, p67, and then challenging with a T. annulata sporozoite stabilate.All the data collected from these two trials indicate that SPAG-1 administered with RWL is better at inducing an effective immune response than SPAG-1 incorporated into ISCOMs, with or without the presence of merozoite antigens (Boulter et al., 1998).
Related Vaccine(s): T. annulata Subunit SPAG-1 Protein Vaccine

3. TA17050 merozoite-piroplasm surface antigen Tams1

Gene Name : TA17050 merozoite-piroplasm surface antigen Tams1
Sequence Strain (Species/Organism) : Theileria annulata
VO ID : VO_0011188
NCBI Gene ID : 3864438
NCBI Protein GI : 84997996
Locus Tag : TA17050
Genbank Accession : AF214915
Protein Accession : XP_953719
Taxonomy ID : 5874
Chromosome No : 1
Gene Starting Position : 371414
Gene Ending Position : 372259
Gene Strand (Orientation) : -
Protein pI : 9.46
Protein Weight : 29651.5
Protein Length : 281

DNA Sequence : Show Sequence

>NW_001091929.1:371414-372259 Theileria annulata strain Ankara isolate clone C9 chromosome 1, *** SEQUENCING IN PROGRESS ***
TTTAAAGGAAGTAAAGGACTGATGAGAAGACGATGAGTACTGAGGCGAAGACTGCAAGGGGGGAGAACTT
GTCGACAACTGGTTTGTAATCGGTTGACCAGGATGAGTTCATGGCATTCAAGGCCTTGTTTGCATCTGCC
TGTGTCATTTGAACCCACTTATCGTCCTTAAGCTCGAAGTAGGTCTCCTTCAACCTTGAGTCACCGGTAT
AGAAGTAGTAGAGTTTGACGAACTTCTTGGAATCAGAACCAACAAAAACAACAACTTCAAGATACTTGGC
ATTGTTTGGTTTTCCGACTTCTTTCTTGTCGAAGGTGACTTTGGAAGGTTTAAATTCCTTTTTAAAGGTG
TACATCTTTCCAGTGCCGAAGGCGGAGGAGGTGAACAAAGATGTATCTTCGAACTTGGAAGCATCTAGTT
CCTTGGCGGATTTTCCCTTGAACAAGACATCATCGTAGTAGGTCTCGAATTTGACCTCAGAATATTCCTT
GTCTCCCTTCTTCTTGAACATCTTTGGCTGGGCAGGGTGAAGATTAAGTCTGAACCACTCATCGGATTCA
TGCTTAAGTTTGAATGCCTGTACTGGGGTATGTTTTGAGGTGTCAACATTGAACAAGGTCTTGTCTCCGA
CCTTAAGGGTCTTGAAACGGTAGCCATCCGCGACAGTTAACTCAGTGGTGTTAGAGTCGACGTTTTTAAA
GGTTACATTCTCACATGAAGTGAGAGTAACATCAAGAACAACATCTTTTTTTTCCTCCTTTTTCTTTTCA
TCCTCATTTGCAGCATTAACGGATGAGATAACGAAGAAGCTCAAATATAAGAACTTGAGGGTGGTCCTGG
ACAACA

Protein Sequence : Show Sequence

>XP_953719.1 merozoite-piroplasm surface antigen Tams1 [Theileria annulata]
MLSRTTLKFLYLSFFVISSVNAANEDEKKKEEKKDVVLDVTLTSCENVTFKNVDSNTTELTVADGYRFKT
LKVGDKTLFNVDTSKHTPVQAFKLKHESDEWFRLNLHPAQPKMFKKKGDKEYSEVKFETYYDDVLFKGKS
AKELDASKFEDTSLFTSSAFGTGKMYTFKKEFKPSKVTFDKKEVGKPNNAKYLEVVVFVGSDSKKFVKLY
YFYTGDSRLKETYFELKDDKWVQMTQADANKALNAMNSSWSTDYKPVVDKFSPLAVFASVLIVFSSVLYF
L

Molecule Role : Protective antigen
Molecule Role Annotation : To test the potential of subunit vaccines against T. annulata infection, we immunized four groups of three calves with either recombinant (re-) (Tams1-1 and Tams1-2) proteins or naked DNA encoding these antigens. All calves vaccinated with ISCOMs proved to be protected from T. annulata infection and had generated antibodies against both re-(Tams1-1 and Tams1-2) at the time of challenge (d'Oliveira et al., 1997).
Related Vaccine(s): T. annulata Tams1 Protein Vaccine

III. Vaccine Information

1. T. annulata Subunit SPAG-1 Protein Vaccine

a. Vaccine Ontology ID:

VO_0011517

b. Type:

Subunit vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

cow

e. Gene Engineering of spag-1

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

f. Adjuvant:

VO ID: VO_0001267
Description: RWL, a proprietary saponin-based adjuvant supplied by SmithKline Beecham (Boulter et al., 1998)

g. Immunization Route

Intramuscular injection (i.m.)

h. Cattle Response

Vaccination Protocol: Three immunizations were given at 28 day intervals. The vaccination trials took place at two sites, the Centre for Tropical Veterinary Medicine (CTVM) in Edinburgh and Utrecht University, the Netherlands. The four CTVM groups (groups I, II, III and IV) were immunized with His6-SPAG-1 in RWL, NS1-p67 in RWL, His6-SPAG-1 incorporated into ISCOMs and PBS-RWL control, respectively, at the doses indicated. RWL is a proprietary saponin-based adjuvant supplied by SmithKline Beecham. The NS1-p67 has been previously described 8 and was supplied by collaborators at ILRI, Nairobi, Kenya. The four groups of cattle at Utrecht University (groups V, VI, VII and VIII) were immunized with His6-SPAG-1, His6-TAMS 1-1/1-2, His6-SPAG-1 plus TAMS 1-1/1-2, all incorporated into ISCOMs and an ISCOM control, at the doses indicated (Boulter et al., 1998).
Challenge Protocol: Fourteen days after the third immunization all the calves were challenged with an ∼LD50 (0.2 tick equivalents) of the same T. annulata Hissar sporozoite stabilate.
Efficacy: All the data collected from these two trials indicate that SPAG-1 administered with RWL is better at inducing an effective immune response than SPAG-1 incorporated into ISCOMs, with or without the presence of merozoite antigens. The SPAG-1 RWL group appeared to be the best protected to challenge. The prepatent period in this group, i.e. the time to when the first macroschizont is seen in lymph node smears, is significantly increased compared to controls, as is the incubation period. Furthermore, 3 of the animals in this group survived challenge (Boulter et al., 1998).

2. T. annulata Tams1 Protein Vaccine

a. Vaccine Ontology ID:

VO_0004181

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of TA17050 merozoite-piroplasm surface antigen Tams1

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

e. Adjuvant:

VO ID: VO_0000757
Description: Immunostimulating complexes (ISCOMs) (d'Oliveira et al., 1997).

f. Immunization Route

Intramuscular injection (i.m.)

g. Cattle Response

Vaccination Protocol: Calves were immunized via intramuscular injection with 1 ml ISCOM vaccine given intramuscularly, containing 20 μg re-(Tamsl-l or Tams1 -2) (d'Oliveira et al., 1997).
Challenge Protocol: Calves were challenged with T. annulata Ankara strain (d'Oliveira et al., 1997).
Efficacy: All calves vaccinated with ISCOMs proved to be protected from T. annulata infection and had generated antibodies against both re-(Tams1-1 and Tams1-2) at the time of challenge (d'Oliveira et al., 1997).

3. T. annulata vaccine by Local veterinary institutes

a. Manufacturer:

Local veterinary institutes

b. Vaccine Ontology ID:

VO_0011476

c. Type:

Live, attenuated vaccine

d. Status:

Research

e. Host Species for Licensed Use:

Cattle

f. Immunization Route

g. Description

Culture-derived schizonts(Shkap and Pipano, 2000). Host speices also include Theileria hirci.

IV. References

1. Boulter et al., 1998: Boulter NR, Brown CG, Kirvar E, Glass E, Campbell J, Morzaria S, Nene V, Musoke A, D'Oliveira C, Gubbels MJ, Jongejan F, Hall FR. Different vaccine strategies used to protect against Theileria annulata. Annals of the New York Academy of Sciences. 1998; 849; 234-246. [PubMed: 9668470].

2. d'Oliveira et al., 1997: d'Oliveira C, Feenstra A, Vos H, Osterhaus AD, Shiels BR, Cornelissen AW, Jongejan F. Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems. Vaccine. 1997; 15(16); 1796-1804. [PubMed: 9364686].

3. Pipano and Shkap, 2000: Pipano E, Shkap V. Vaccination against tropical theileriosis. Annals of the New York Academy of Sciences. 2000; 916; 484-500. [PubMed: 11193663].

4. Schnittger et al., 2002: Schnittger L, Katzer F, Biermann R, Shayan P, Boguslawski K, McKellar S, Beyer D, Shiels BR, Ahmed JS. Characterization of a polymorphic Theileria annulata surface protein (TaSP) closely related to PIM of Theileria parva: implications for use in diagnostic tests and subunit vaccines. Molecular and biochemical parasitology. 2002; 120(2); 247-256. [PubMed: 11897130].

5. Shkap and Pipano, 2000: Shkap V, Pipano E. Culture-derived parasites in vaccination of cattle against tick-borne diseases. Annals of the New York Academy of Sciences. 2000; 916; 154-171. [PubMed: 11193616].

6. Wiki: T. annulata: Wiki: T. annulata [http://en.wikipedia.org/wiki/Theileria_annulata]