Theileria parva 5875 The sporozoite develops in the salivary glands of the vector and is introduced into the mammalian host during tick feeding. Sporozoites rapidly enter lymphocytes by a receptor-mediated process and differentiate into schizonts. After several cycles of multiplication, a proportion of schizonts undergo merogony to produce merozoites, which invade erythrocytes and develop into piroplasms, the infective stage for ticks. The disease is characterized by pyrexia, generalized lymphadenopathy, and leukopenia (Musoke et al., 1992). East Coast Fever Cattle that recover from ECF develop solid, strain-specific immunity that lasts for several years. Experiments have shown that passive transfer of antibodies to the schizont and piroplasm stages from immune to naïve cattle is not protective. There is now strong evidence that protective immunity is mediated by the generation of MHC class I restricted cytotoxic T cells (CTLs) specific for schizont-infected lymphocytes (Morzaria et al., 2000). The African buffalo plays an important role in the epidemiology of the disease since it is a natural host that does not suffer from the disease but remains a constant source of infection for ticks. The disease that occurs in cattle after the introduction of T. parva from buffalo is referred to as corridor disease, and is characterized by high mortality and low parasitosis (Morzaria et al., 2000). Theileria parva, a tick transmitted protozoan parasite, causes a severe lymphoproliferative disease in cattle variously known as East Coast fever, January disease or corridor disease. The main vector of the parasite is a three-host tick Rhipicephalus appendiculatus. The disease is present in 10 countries in Eastern and Central Africa, however the vector is more widely distributed than the parasite and there is a potential danger of the disease spreading to other areas. Theileria parva is highly pathogenic to cattle and mortality in Bos taurus cattle and their crosses can approach 100%. The parasite is considered to be the major factor in inhibiting the introduction of highly productive taurine breeds of cattle in sub-Saharan Africa. Where such cattle are maintained successfully in Africa, it is through heavy cost to the farmer, involving the use of toxic and expensive chemicals to kill the vector. Estimated annual losses are around US$190 million. The most common form of the disease in cattle due to T. parva is East Coast fever (ECF). It is characterized by high mortality in exotic cattle and large numbers of schizonts and piroplasms. A mild form of the disease, known as January disease, occurs predominantly in Zimbabwe. This disease occurs seasonally, and the outbreaks, coinciding with the emergence from diapause of adult ticks in January, are usually characterized by high morbidity and low mortality with low numbers of parasites. The main vector of January disease is Rhipicephalus zambesiensis (Morzaria et al., 2000). 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. parva Subunit p67 Protein Vaccine VO_0011494 Subunit vaccine Research Subcutaneous Injection Subcutaneous Injection Recombinant protein preparation The immunization regimen consisted of five inoculations in 2-ml vol containing 1 mg of recombinant p67 emulsified in 3% saponin (Merck) and administered subcutaneously at monthly intervals (Musoke et al., 1992). Immunization with p67 induced protection in 70% of the immunized cattle (Musoke et al., 1992). Immunized groups were challenged 10 days after the final inoculation along with four nonimmunized control animals. In both experiments, the nonimmunized controls served to test the infectivity of the sporozoite stabilate (Musoke et al., 1992). Theileria parva vaccine by Centre for Ticks and Tickborne Disease, Malawi Centre for Ticks and Tickborne Disease, Malawi VO_0011475 Live, attenuated vaccine Research NA Infection followed by drug treatment(Boulter and Hall, 1999) NA p67 Theileria parva strain Mugaga VO_0011183 4106806 CDD:253298 5875 + p67 surface antigen 4.7 70967 771 Sporozoite P67 surface antigen; pfam05642 >AAD03021.1 p67 surface antigen [Theileria parva] MQITQFLLIIPVFFVSAGDKMPTEEQPFPSRLGPLVTLESAITQPTPVYTMRTVGNVSKAAKVWKSAVSS PDVSTTILTPVSEENITSTLQTQTEEVPAASGSDSSRATNLVQTQSQVQDNVKQQQDTKGNRSDSEEENE DGTLSTDVSPAIPTPVSEEIITPTLQAQTKEEVPPADLSDQVPSNGSDSEEEDEDSSLGTDERGLKKTLP PGKTSTGETTSDQDLKTKQQKNGVSGPAGGSHSSGLKVPGLGVPGEVSPQGGQSLASNTSREGQTQHHQV RDGDGRVIEPKIGLPGPPSAPEPSPGAPGIKVRESGNRAMDIVQFLGRFRPEPRAYEGERTNVAELKKFL FEELESLVNTLIELKLAIANDFVEITDGLRKNTKDHEARLKLLTGVEFTKRKSAANVVKGFSSLYCVLLM NMNVIKEKTKESEVADGIWKLSTIPDKVANELLLAMEKIVVPPKTPELDEAFKEIEFGFKIAYYATKDIL SSIENTVHNLMHAKNYEENFIAQVRNSLRMVPHQMNLTESSFVIKISDMMRRRGTASQDEPAGAGSGVTP GRGSSGTPGAAGTGGGSLRGFDLSEEEVKKILDEIVKDPSDGELGLGDLSDPSGRSSGRQPSLGPSLGIT DGQAGPTIVSPTGPTIAAGGEQPPSAPNGTATGPAGTQPEGGEKKEGLIQKLKKKLLGSGFEVASLMIPM ATIIISIVH Protective antigen Immunization with recombinant forms of a sporozoite surface antigen (r-p67), derived from either bacterial or insect cells, induces high levels of sporozoite neutralizing antibodies in cattle.In vivo immunization studies have shown that approximately 30% of immunized cattle are nonreactors to a needle LD70 sporozoite challenge, 40% experience a mild disease reaction from which they recover, and the remaining 30% suffer severe disease and are clinically indistinguishable from controls. Transient parasitosis and mild clinical reactions are also observed in challenge of cattle immunized by infection and treatment and such responses constitute immunity to ECF. Hence, p67 is able to routinely induce immunity at a level of about 70% [Ref1196:Morzaria et al., 2000]. Boulter and Hall, 1999 journal Boulter N, Hall R 1999 44 41-97 Advances in parasitology Graham et al., 2006 journal Graham SP, Pellé R, Honda Y, Mwangi DM, Tonukari NJ, Yamage M, Glew EJ, de Villiers EP, Shah T, Bishop R, Abuya E, Awino E, Gachanja J, Luyai AE, Mbwika F, Muthiani AM, Ndegwa DM, Njahira M, Nyanjui JK, Onono FO, Osaso J, Saya RM, Wildmann C, Fraser CM, Maudlin I, Gardner MJ, Morzaria SP, Loosmore S, Gilbert SC, Audonnet JC, van der Bruggen P, Nene V, Taracha EL 2006 103 9 3286-3291 Proceedings of the National Academy of Sciences of the United States of America Morzaria et al., 2000 journal Morzaria S, Nene V, Bishop R, Musoke A 2000 916 464-473 Annals of the New York Academy of Sciences Musoke et al., 1992 journal Musoke A, Morzaria S, Nkonge C, Jones E, Nene V 1992 89 2 514-518 Proceedings of the National Academy of Sciences of the United States of America