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Anti-protozoal vaccine

A technology of immunotherapy and immunogenic fragments, applied in the field of immunotherapy of protozoal diseases, which can solve the problems of the complex life cycle of Plasmodium and unidentified T cells.

Inactive Publication Date: 2005-08-03
COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the complex life cycle of Plasmodium makes the identification of this protein a daunting task
[0009] Although there is good evidence that different effector components of the adoptive immune system mediate immunity to blood-stage Plasmodium (Freeman & Parish, 1981; Grun & Weidanz, 1983; Brake et al, 1988; Seixas & Langhorne, 1999), but the main component of the target antigen, the effector CD4 + T cells have not yet been identified

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0131] Example 1 Identification of HXGPRT as an immunogen in Plasmodium yoelii

[0132] 1. Materials and methods

[0133] mouse

[0134] 4-6 week-old normal BALB / c mice, athymic BALB / c nude mice and BALB / c SCID mice were purchased from Animal Resources Center (Perth, WA, Australia) and kept under specific pathogen-free conditions (specific- Pathogen-free) were kept in the animal facility (animal facility) of QIMR. At 6-8 weeks of age they were used for testing.

[0135] parasite

[0136] Rodent Plasmodium yoelii 17XNL was carried out between infected and uninfected mice by the intraperitoneal route (i.p.) 6 Alternate passages of parasite-infected red blood cells (pRBC) / mice were maintained. After 3 or 4 passages, stable parasites were then frozen and stored in liquid nitrogen. Cryopreserves were subjected to three alternate passages before being used for experimental challenge infection. Parasites were collected from blood obtained by cardiac puncture and tail docking a...

Embodiment 2

[0186] Example 2 Mapping the T cell epitope of HGXPRT

[0187] The data in Example 1 have established that Plasmodium HGXPRT may play a role in modulating protection against malaria infection. Since mammals also express HGXPRT, and mammalian HGXPRT is quite homologous to parasite HGXPRT (Fig. 6), it was important to identify the minimal non-homologous regions of the protein that might be targets of protective T cells. These regions may be used as malaria vaccine candidates.

[0188] To this point, 24 linear overlapping peptides spanning HGXPRT were designed to define protein regions containing protective T cell epitopes (Figure 7). Various strains of mice were immunized with the full-length P. falciparum HGXPRT protein (PfHGXPRT) or peptide pools from PfHGXPRT to determine protein regions that generate proliferative T cell responses. Afterwards, these regions (corresponding to the peptides) were then used to immunize mice to determine whether the corresponding T cells could ...

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Abstract

Immunotherapy of protozoal diseases is provided by use of hypoxanthine guanine xanthine phosphoribosyl transferase protein, or peptide fragments thereof, as an immunogen in vaccines effective against protozoal diseases such as malaria and babesiosis. In particular, immunization with hypoxanthine guanine xanthine phosphoribosyl transferase or peptide fragments thereof, induces T cell immunity to blood stage malaria. In particular embodiments, the invention provides protein and DNA malaria vaccines and methods of prophylactic and therapeutic immunization that elicit T cell-mediated immune responses broadly applicable to protozoal diseases including malaria.

Description

technical field [0001] The present invention relates to immunotherapy for protozoan diseases. More specifically, the present invention relates to the use of hypoxanthine guanine xanthine phosphoribosyl transferase (hypoxanthine guanine xanthine phosphoribosyl transferase) protein or a peptide fragment thereof as an immunogen in a vaccine effective against protozoan diseases such as malaria and Babesiosis. The surprising aspect of the present invention is that immunization with hypoxanthine-guanine xanthine phosphoribosyltransferase protein or peptide fragments thereof induces T cell immunity against blood stage malaria. Thus, the present invention provides proteinaceous and DNA malaria vaccines that are broadly applicable to protozoan diseases, including malaria, and methods of prophylactic and therapeutic immunization to generate T cell-mediated immune responses. Background technique [0002] In general, protozoan diseases seriously affect the health and survival of human...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7105A61K31/711A61K38/10A61K38/45A61K39/00A61K39/015A61K39/018A61P33/06C07H21/02C07H21/04C07K14/44C07K14/445C07K16/20C12N5/06C12N5/08C12N9/10
CPCC12N9/10A61K39/00C07K14/445C07K16/20A61P33/06Y02A50/30A61K39/46A61K39/4611A61K2239/31A61K39/4644A61K39/464714
Inventor 莫里斯·马克邦戈乔治·艾尔弗雷德·赖丁彼得·维拉德森迈克尔·古德
Owner COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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