Monoclonal antibody neutralizes the sporozoite stage of different <i>Theileria parva</i> stocks

Dobbelaere, Dirk; Spooner, P.R.; Barry, W.C.; Irvin, A.D.

doi:10.1111/j.1365-3024.1984.tb00808.x

Cited by 82 publications

(43 citation statements)

References 21 publications

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“…The observations of Musoke and his colleagues (58,59) that serum from cattle which had been challenged repeatedly with sporozoites was capable of neutralising sporozoite infectivity in vitro and in vivo, and that this activity was crossreactive between stocks, prompted a search for sporozoite surface antigens which might mediate this activity. By generating MAB with neutralising activity (25,59), it has been possible to identify a neutralising antigen on the surface of the sporozoite. This molecule, of relative molecular mass (Mr) 67 kiloDaltons (kD), is specific to the sporoblast and sporozoite stages of the parasite, and appears to be invariant between strains.…”

Section: The Search For Parasite Antigensmentioning

confidence: 99%

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

McKeever¹,

Morrison²

1990

Rev. Sci. Tech. OIE

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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...

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Section: The Search For Parasite Antigensmentioning

confidence: 99%

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

McKeever¹,

Morrison²

1990

Rev. Sci. Tech. OIE

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“…Monoclonal antibodies directed against p67 block (Dobbelaere et al 1984), and soluble p67 competitively inhibits invasion of bovine lymphocytes by the sporozoites. P67 contains 709 amino acid residues and has the characteristics of a transmembrane protein.…”

Section: Introductionmentioning

confidence: 99%

Fusion to green fluorescent protein improves expression levels of Theileria parva sporozoite surface antigen p67 in insect cells

et al. 2002

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S U M M A R YEast Coast fever (ECF) is a fatal disease of cattle caused by the protozoan parasite Theileria parva. The development of a subunit vaccine, based on the sporozoite-specific surface antigen p67, has been hampered by difficulties in achieving highlevel expression of recombinant p67 in a near-authentic form. Therefore two sets of recombinant baculovirus vectors were constructed. The first set, encoding various regions of p67, produced low levels of the corresponding p67 domains in High Five TM cells, despite the presence of large amounts of p67 RNA. The second, consisting of p67 domains fused to the carboxy-terminus of GFP expressed significantly higher levels of p67 protein. The GFP : p67 fusion proteins were recognized by a sporozoite-neutralizing monoclonal antibody (TpM12) raised against native p67 whereas non-fused full length p67 expressed in insect cells was not recognized. GFP-tagging therefore, appeared to enhance the stability of p67 and to conserve its folding. The high-level expression of p67 domains in a more authentic form is an important step towards the development of an effective subunit vaccine against ECF.

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“…Antibodies to the main sporozoite surface antigen, p67, also neutralized sporozoite entry (7,8). Since purified p67 could inhibit binding (5), the molecule can be considered the sporozoite ligand.…”

mentioning

confidence: 98%

Role of the Polymorphic Immunodominant Molecule in Entry of Theileria parva Sporozoites into Bovine Lymphocytes

2014

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Theileria parva is a tick-transmitted apicomplexan parasite that infects cattle and African buffalo. In cattle, it causes a fatal lymphoproliferative disease called East Coast fever. The polymorphic immunodominant molecule (PIM) is expressed by two stages of the parasite: the sporozoite, which is inoculated by the tick to infect mammalian lymphocytes, and the schizont, the established intralymphocytic stage. Here, we demonstrate that monoclonal antibodies (MAb) to PIM can reduce the ability of sporozoites to infect bovine lymphocytes in vitro. This reduction appears to be due to blocking of sporozoite attachment by binding of the MAb to several regions of PIM. Interestingly, one MAb, which recognizes an epitope in the central variable region of PIM, did not inhibit sporozoite infectivity. We also demonstrate that PIM antigen, as a recombinant molecule, can also reduce sporozoite infectivity in vitro by blocking both attachment and internalization of sporozoites. Electron microscopic studies showed that PIM is present in microspheres below the sporozoite surface and is transported to the parasite surface soon after contact with bovine lymphocytes. The results suggest that at least two sporozoite molecules, PIM and the previously described p67, are involved in the entry of T. parva into mammalian lymphocytes.

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Monoclonal antibody neutralizes the sporozoite stage of different Theileria parva stocks

Cited by 82 publications

References 21 publications

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

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

Fusion to green fluorescent protein improves expression levels of Theileria parva sporozoite surface antigen p67 in insect cells

Role of the Polymorphic Immunodominant Molecule in Entry of Theileria parva Sporozoites into Bovine Lymphocytes

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