VIOLIN: Vaccine Investigation and Online Information Network

Theileria parva

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. p67 (Protective antigen)
2. Tp1 (Protective antigen)
3. Tp2 (Protective antigen)
Vaccine Information
1. T. parva Subunit p67 Protein Vaccine
2. Theileria parva vaccine by Centre for Ticks and Tickborne Disease, Malawi
References

I. General Information

1. NCBI Taxonomy ID:

5875

2. Disease:

East Coast Fever

3. Introduction

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).

4. Microbial Pathogenesis

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).

5. Host Ranges and Animal Models

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).

6. Host Protective Immunity

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).

II. Vaccine Related Pathogen Genes

1. p67

Gene Name : p67
Sequence Strain (Species/Organism) : Theileria parva strain Mugaga
VO ID : VO_0011183
NCBI Protein GI : 4106806
Other Database IDs : CDD:253298
Taxonomy ID : 5875
Gene Strand (Orientation) : +
Protein Name : p67 surface antigen
Protein pI : 4.7
Protein Weight : 70967
Protein Length : 771
Protein Note : Sporozoite P67 surface antigen; pfam05642

Protein Sequence : Show Sequence

>AAD03021.1 p67 surface antigen [Theileria parva]
MQITQFLLIIPVFFVSAGDKMPTEEQPFPSRLGPLVTLESAITQPTPVYTMRTVGNVSKAAKVWKSAVSS
PDVSTTILTPVSEENITSTLQTQTEEVPAASGSDSSRATNLVQTQSQVQDNVKQQQDTKGNRSDSEEENE
DGTLSTDVSPAIPTPVSEEIITPTLQAQTKEEVPPADLSDQVPSNGSDSEEEDEDSSLGTDERGLKKTLP
PGKTSTGETTSDQDLKTKQQKNGVSGPAGGSHSSGLKVPGLGVPGEVSPQGGQSLASNTSREGQTQHHQV
RDGDGRVIEPKIGLPGPPSAPEPSPGAPGIKVRESGNRAMDIVQFLGRFRPEPRAYEGERTNVAELKKFL
FEELESLVNTLIELKLAIANDFVEITDGLRKNTKDHEARLKLLTGVEFTKRKSAANVVKGFSSLYCVLLM
NMNVIKEKTKESEVADGIWKLSTIPDKVANELLLAMEKIVVPPKTPELDEAFKEIEFGFKIAYYATKDIL
SSIENTVHNLMHAKNYEENFIAQVRNSLRMVPHQMNLTESSFVIKISDMMRRRGTASQDEPAGAGSGVTP
GRGSSGTPGAAGTGGGSLRGFDLSEEEVKKILDEIVKDPSDGELGLGDLSDPSGRSSGRQPSLGPSLGIT
DGQAGPTIVSPTGPTIAAGGEQPPSAPNGTATGPAGTQPEGGEKKEGLIQKLKKKLLGSGFEVASLMIPM
ATIIISIVH

Molecule Role : Protective antigen
Molecule Role Annotation : 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% (Morzaria et al., 2000).
Related Vaccine(s): T. parva Subunit p67 Protein Vaccine

2. Tp1

Gene Name : Tp1
Sequence Strain (Species/Organism) : Theileria parva
NCBI Protein GI : AIA64008
Taxonomy ID : 5875
Protein Name : CD8+ T cell target antigen Tp1
Protein pI : 5.14
Protein Weight : 14555.64
Protein Length : 207

Protein Sequence : Show Sequence

>AIA64008.1 CD8+ T cell target antigen Tp1, partial [Theileria parva]
AFAADPGFCYFLLIPGPDSKPIFFKNDGDKFLRCVGYPKVKEEMLEMATKFNRLPKGVEIPAPPGVKPEA
PTPTPTTITPSVPPTIPTPITPSAPPTTPPTGLNFNLTVQNKFMIGSQEVKLNITHEYEGVYEA

Molecule Role : Protective antigen
Molecule Role Annotation : (Graham et al., 2006)

3. Tp2

Gene Name : Tp2
Sequence Strain (Species/Organism) : Theileria parva
NCBI Protein GI : AIA64020
Taxonomy ID : 5875
Protein Name : CD8+ T cell target antigen Tp2
Protein pI : 7.53
Protein Weight : 18608.89
Protein Length : 241

Protein Sequence : Show Sequence

>AIA64020.1 CD8+ T cell target antigen Tp2, partial [Theileria parva]
ISLYFIIYILHSPVLGGNCSHEELKKLGMLEGDGFDRDALFKSSHGMGKVGKRYGLKTTPKAEKVLTDLE
TLFGKHGLAGISKDCLKCFAQSLVCVLMKCRGACLKGPCTDDCQNCFDTNCKSALLECIGKPSIPNPCKW
KEDYLKYKFPETDEDESTKKGEASGTS

Molecule Role : Protective antigen
Molecule Role Annotation : (Graham et al., 2006)

III. Vaccine Information

1. T. parva Subunit p67 Protein Vaccine

a. Vaccine Ontology ID:

VO_0011494

b. Type:

Subunit vaccine

c. Status:

Research

d. Gene Engineering of p67

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

e. Adjuvant:

VO ID: VO_0001267

f. Immunization Route

Subcutaneous Injection

g. Cattle Response

Vaccination Protocol: 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).
Challenge Protocol: 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).
Efficacy: Immunization with p67 induced protection in 70% of the immunized cattle (Musoke et al., 1992).

2. Theileria parva vaccine by Centre for Ticks and Tickborne Disease, Malawi

a. Manufacturer:

Centre for Ticks and Tickborne Disease, Malawi

b. Vaccine Ontology ID:

VO_0011475

c. Type:

Live, attenuated vaccine

d. Status:

Research

e. Host Species for Licensed Use:

Cattle

f. Immunization Route

g. Description

Infection followed by drug treatment(Boulter and Hall, 1999)

IV. References

1. Boulter and Hall, 1999: Boulter N, Hall R. Immunity and vaccine development in the bovine theilerioses. Advances in parasitology. 1999; 44; 41-97. [PubMed: 10563395].

2. Graham et al., 2006: Graham SP, Pell� 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. Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(9); 3286-3291. [PubMed: 16492763].

3. Morzaria et al., 2000: Morzaria S, Nene V, Bishop R, Musoke A. Vaccines against Theileria parva. Annals of the New York Academy of Sciences. 2000; 916; 464-473. [PubMed: 11193661].

4. Musoke et al., 1992: Musoke A, Morzaria S, Nkonge C, Jones E, Nene V. A recombinant sporozoite surface antigen of Theileria parva induces protection in cattle. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89(2); 514-518. [PubMed: 1731322].