Theileria parva : the nature of the immune response and its significance for immunoprophylaxis

Abstract

Summary: Theileria parva is a tick-borne haemoprotozoan parasite of cattle and buffalo which is responsible for considerable economic losses to cattle farming in Eastern, Central and Southern Africa. Infection with the parasite results in an acute lymphoproliferative disorder with high mortality, but animals which survive infection are solidly immune to homologous challenge. Such immunity can be reproduced by infecting cattle with the parasite and treating them with tetracyclines or theilericidal drugs, but the widespread use of this technique as a method of control is hindered by its dependence on live parasites which require cryopreservation for maintenance and can give rise to carrier States. In addition, cross-protection between different strains of the parasite is not absolute. These problems have prompted a search for methods of immunisation based on the use of inactivated parasites or their derivatives. Such efforts have met with consistent failure, however, and in recent years scientists have adopted the more rational approach of defining the immune responses of cattle to the parasite with a view to identifying the parasite components which provoke them. These studies have revealed that protection is likely to be mediated by parasitespecific cytotoxic T cells which are restricted by class I major histocompatibility complex (MHC) products. The significance of this observation to the development of an effective subunit vaccine is discussed in the light of current knowledge of the inductive requirements of cytotoxic T cells.KEYWORDS: Antibody -Antigen -Antigen delivery -Antigen processingCell-mediated immunity -Cross-protection -Immunisation -Immunity -MHCrestriction -Parasite -Pathology -Theileria -Vaccine. THE PARASITE AND ITS LIFE CYCLETheileria parva is a haemoprotozoan parasite which infects cattle and buffalo in large areas of Eastern, Central and Southern Africa. The sporozoite stage of the parasite is transmitted by the three-host tick Rhipicephalus appendiculatus and invades lymphocytes, where its development to the schizont stage is associated with uncontrolled proliferation of the cell. The capacity of the parasite to associate with the mitotic spindle (78) ensures that schizonts are passed on to successive generations of daughter cells, giving rise to a clonal expansion of the initially parasitised population. A proportion of parasitised cells undergo merogony, resulting in disruption of the lymphocyte and release of merozoites into the blood. Merozoites then invade erythrocytes and differentiate into piroplasms which constitute the infective stage for the tick. PATHOGENESISInfection of cattle with T. parva gives rise to an acute lymphoproliferative disorder known as East Coast fever (ECF), and the course of this disease has been well characterised in experimentally-infected animals (47). At approximately 8 days after infection, schizont-infected cells are detectable in the lymph node which drains the site of inoculation. Parasitised cells can be detected in other lymphoid tissues throughout th...

The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

“…The vectors are ticks within the genus Rhipicephalus, mainly R. appendiculatus, and the primary mammalian host is the African Cape buffalo ( Syncerus caffer ). While the African buffalo is an asymptomatic carrier of T. parva , cattle are evolutionarily recent hosts and typically succumb rapidly to the disease [ 1 ]. The parasite, which is transmitted as a sporozoite during tick feeding, invades lymphocytes of buffalo and cattle.…”

Combining landscape genomics and ecological modelling to investigate local adaptation of indigenous Ugandan cattle to East Coast fever

“…A specific adaptive response towards T. parva parva infection may have evolved in south-western Uganda, possibly due to ecological conditions suitable for the parasite survival, and to the presence of a more tick-susceptible cattle population (S10 Fig.). Theileria parva parva pathogenicity is linked to its ability to invade host lymphocytes, and promoting their transformation and clonal expansion through the activation of several host-cell signalling pathways [15,75,122]. Here, we found seven markers significantly associated with γ , two of which (ARS-110102 and ARS-24867) included within SLA 2 genic region on chromosome 13 (S13 Fig.).…”

Delivery of the p67 Sporozoite Antigen of Theileria parva by Using Recombinant Salmonella dublin : Secretion of the Product Enhances Specific Antibody Responses in Cattle

“…For this reason and because variation has been observed among cattle in the dose of sporozoites required to produce severe disease (4), it is possible that complete herd protection will not be achieved through immu-nization with p67 alone. It is known that animals that recover from ECF are protected by virtue of class I major histocompatibility complex-restricted cytotoxic T lymphocytes specific for schizont-infected cells (19). An intensive search for the parasite antigens that provoke these responses is under way, with a view to the development of a second-generation subunit vaccine with broader protective capacity.…”

“…Sporozoites enter lymphocytes through a receptor-mediated process and rapidly differentiate into schizonts, an event that is associated with transformation of the infected cell to a state of uncontrolled proliferation. Subsequent invasion of nonlymphoid tissues by parasitized cells and the associated immunopathological effects usually result in death of the animal within 3 weeks of infection (19). Animals that recover from the disease are solidly immune to homologous challenge and exhibit both neutralizing antibodies against the sporozoite stage and cell-mediated responses to the schizont-infected cell (5,9,20).…”