Theileria annulata 5874 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). Theileriosis 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). 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). 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). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 T. annulata Subunit SPAG-1 Protein Vaccine VO_0011517 Subunit vaccine Research Intramuscular injection (i.m.) RWL, a proprietary saponin-based adjuvant supplied by SmithKline Beecham (Boulter et al., 1998). Intramuscular injection (i.m.) Recombinant protein preparation 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). 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). 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. T. annulata Tams1 Protein Vaccine VO_0004181 Subunit vaccine Research Intramuscular injection (i.m.) Immunostimulating complexes (ISCOMs) (d'Oliveira et al., 1997). Intramuscular injection (i.m.) Recombinant protein preparation 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). 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). Calves were challenged with T. annulata Ankara strain (d'Oliveira et al., 1997). T. annulata vaccine by Local veterinary institutes Local veterinary institutes VO_0011476 Live, attenuated vaccine Research NA Culture-derived schizonts(Shkap and Pipano, 2000). Host speices also include Theileria hirci. NA spag-1 Theileria annulata VO_0011187 161885 CDD:253298 5874 ? sporozoite surface antigen 4.77 83569.63 981 Sporozoite P67 surface antigen; pfam05642 >AAA30134.1 sporozoite surface antigen [Theileria annulata] MNIIHFLLTIPAIFVSGADKMPAGESSRTSKPSPLVTLESAVTQPSKDPFKTISALSKATKVWKSAVSVS GDSKTVPTPVSEPMITRSFQEPVSQELEFQSDTEINESGSGSDEDEDDDDDEEEEEDDKSTSSKNGKGSP KAQPGVSSSSTSSASPTSPTTTLSQTGLGPSGSHAQQDPGVGVPGVGVPGVGVPGVGVPGVGVPGVGVPG VGGVPGVGVAPGVGVPGVGVAPGVGVGADSSGLPGSGGLGAGAKAGKGQGSGLQGPGGVGVVPGVGVAAS SSSPGKPPGVGAGVMPGVGVRAQGGVIIGAPGVAGVPGGKPGQPVSQELELKSDTEINESGSSSEGEDDD DEEEEEENKSTSSKGAGGKAGKGQGSVSPGGGSSASQTSPTTTPQSGLASSGSHAQQSPQQDPAPSKPSG GGVPGVGVPGVGVPGVGVPGVGVAPGVGVVPGVGGATTSSSSTTSTSTSTTTTTTTSSGKPSDQGSHGTS PRNAVTRQTDSISGPIPSPGDPRAITGQMGEGERFAVQFLGDFKPKPRRYEGQGTDAVKLKQFIFEEVKS LVQTLINLKLAIANDFVEISEKLKKKNQNYVPKLKLLKGEQFDTKQKVANVLKGFNSLYFVFFMNLNLAK EVNKPEELAEFLWKLNTIPDKVGREFELAIEKTKGSEKKKELEEAFNSIGLGFKIAQYATNDILSSITNS VYSLIKLKNFGDDFVTEVRKSLQMVPHQKNLNGSAFIVKISEIINKKGTEDQDQTSGSGSKGTEGGSLRG QDLTEEEVLKVLDELVKDVSEEHVGIGDLSDPSSRTPNAKPAELGPSLVIQNVPSDPSKVTPTQPSNLPQ VPTTGPGNGTDGTTTGPGGNGEGGKDLKEGEKKEGLFQKIKNKLLGSGFEVASIIIPMTTIIFSIVH Protective antigen 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 [Ref1199:Boulter et al., 1998]. TA17050 merozoite-piroplasm surface antigen Tams1 Theileria annulata VO_0011188 3864438 84997996 TA17050 AF214915 XP_953719 5874 1 371414 372259 - 9.46 29651.5 281 >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 >XP_953719.1 merozoite-piroplasm surface antigen Tams1 [Theileria annulata] MLSRTTLKFLYLSFFVISSVNAANEDEKKKEEKKDVVLDVTLTSCENVTFKNVDSNTTELTVADGYRFKT LKVGDKTLFNVDTSKHTPVQAFKLKHESDEWFRLNLHPAQPKMFKKKGDKEYSEVKFETYYDDVLFKGKS AKELDASKFEDTSLFTSSAFGTGKMYTFKKEFKPSKVTFDKKEVGKPNNAKYLEVVVFVGSDSKKFVKLY YFYTGDSRLKETYFELKDDKWVQMTQADANKALNAMNSSWSTDYKPVVDKFSPLAVFASVLIVFSSVLYF L Protective antigen 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 [Ref1200:d'Oliveira et al., 1997]. Boulter et al., 1998 journal 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 1998 849 234-246 Annals of the New York Academy of Sciences d'Oliveira et al., 1997 journal d'Oliveira C, Feenstra A, Vos H, Osterhaus AD, Shiels BR, Cornelissen AW, Jongejan F 1997 15 16 1796-1804 Vaccine Pipano and Shkap, 2000 journal Pipano E, Shkap V 2000 916 484-500 Annals of the New York Academy of Sciences Schnittger et al., 2002 journal Schnittger L, Katzer F, Biermann R, Shayan P, Boguslawski K, McKellar S, Beyer D, Shiels BR, Ahmed JS 2002 120 2 247-256 Molecular and biochemical parasitology Shkap and Pipano, 2000 journal Shkap V, Pipano E 2000 916 154-171 Annals of the New York Academy of Sciences Wiki: T. annulata website http://en.wikipedia.org/wiki/Theileria_annulata