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Detection/Measurement Of Malaria Infection Disease Utilizing Natural Immunity By Hemozoin Induction, Screening Of Preventative Or Therapeutic Medicine For Malaria Infection Disease, And Regulation Of Natural Immunity Induction

a malaria infection and natural immunity technology, applied in the field of detection/measurement of malaria infection disease utilizing natural immunity by hemozoin induction, screening of preventative or therapeutic medicine for malaria infection disease, and regulation of natural immunity induction, can solve the problems of human disease and mortality

Inactive Publication Date: 2009-02-12
OSAKA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]Based on these findings, the present inventors found that it is possible to detect and measure malaria infection by detecting and measuring the HZ-induced, TLR9-mediated, and MyD88-dependent innate immune activity, and that the detection and measurement of malaria infection can be used for the diagnosis of malaria infection, and thus the instant invention has been completed. The present inventors also found that it is possible to screen a vaccine for malaria infection or of a preventative or therapeutic agent for malaria infection using the method for detecting and measuring malaria infection by detecting and measuring the HZ-induced innate immune activity, and thus the instant invention has been accomplished. Further, based on the above findings, the present inventors found that it is possible to regulate HZ-induced, TLR-9 mediated, and MyD88-dependent innate immune induction using HZ, synthetic HZ, or derivatives thereof as an adjuvant or immunostimulant. Specifically, the present inventors became the first to demonstrate that hemozoin is a ligand with a selective immune-response control and activation effect which induces Th1 via TLR9-MyD88 dependent pathway but does not activate other TLR families or TRIF dependent pathway which is a MyD88-independent pathway. The instant invention has been accomplished as a result of the above findings.

Problems solved by technology

Malaria infection is the major cause of disease and mortality of humans, especially in the tropical regions of the world.

Method used

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  • Detection/Measurement Of Malaria Infection Disease Utilizing Natural Immunity By Hemozoin Induction, Screening Of Preventative Or Therapeutic Medicine For Malaria Infection Disease, And Regulation Of Natural Immunity Induction
  • Detection/Measurement Of Malaria Infection Disease Utilizing Natural Immunity By Hemozoin Induction, Screening Of Preventative Or Therapeutic Medicine For Malaria Infection Disease, And Regulation Of Natural Immunity Induction
  • Detection/Measurement Of Malaria Infection Disease Utilizing Natural Immunity By Hemozoin Induction, Screening Of Preventative Or Therapeutic Medicine For Malaria Infection Disease, And Regulation Of Natural Immunity Induction

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example 1

Activation of Innate Immune Activity by HZ and the Regulation Thereof

(Materials and Methods)

(Mice)

[0039]Mutant mice (MyD88-, TRIF-, TLR2-, TLR4-, TLR7-, and TLR9-deficient mice) either on a 129 / Ola×C57 / BL6 or C57 / BL6 background were generated as described in literatures (Immunity 9:143-150, 1999; Immunity 11: 443-451, 1999; Nature 408: 740-745, 2000; Nat. Immunol. 3: 196-200, 2002; Science 301: 640-643, 2003). Age-matched groups of wild type mice and mutant mice were used for experiments. For in-vivo studies, 1500 μg HZ purified from P. falciparum culture and synthetic HZ (β-hematin) were injected intraperitoneally into wild-type mice, MyD88− / − mice, or TLR9− / − mice (J. Immunol. 172: 3101-3110, 2004). Sera were collected from tails at 1, 2, 4, and 6 hours for cytokine ELISA.

(Reagents)

[0040]Synthetic CpG oligodeoxynucleotides (ODN) D35 were synthesized and purchased from Hokkaido System Science Co., Ltd. Lipopolysaccharides (LPS) from Salmonella minnesota Re-595, hemin chloride, and ...

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Abstract

The instant invention is to provide a method for detecting and measuring malaria infection utilizing the induction by hemozoin (HZ); a method for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection using the method for detecting and measuring; and a means for regulating the induction of innate immunity using the HZ, synthetic HZ, or derivatives thereof as an adjuvant or immunostimulant. Malaria infection is detected and measured of by detecting and measuring HZ-induced, TLR9-mediated, and MyD88-dependent innate immune activity. The detection and measurement of malaria infection can be used to diagnose malaria infection. The method for detecting and measuring is also used for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection. Further, HZ, synthetic HZ, or derivatives thereof are used as an adjuvant or immunostimulant to regulate HZ-induced innate immune induction.

Description

TECHNICAL FIELD[0001]The instant invention relates to a method for detecting and measuring malaria infection by detecting and measuring TLR9-mediated, MyD88-dependent innate immune activity induced by hemozoin, hydrophobic heme polymers produced as a hemoglobin metabolite by malaria parasites; screening of a vaccine for malaria infection or a preventative or therapeutic agent for malaria infection using the method for detection and measurement; regulation of the induction of innate immunity using the hemozoin or synthetic hemozoin as an adjuvant or immunostimulant; a TLR9 agonist containing hemozoin, synthetic hemozoin or derivatives thereof as an active ingredient; and the like.BACKGROUND ART[0002]Malaria infection is the major cause of disease and mortality of humans, especially in the tropical regions of the world. Due to a complex life cycle and rapid polymorphism of malaria parasites, host-parasite interactions and resulting innate immune responses to malaria parasites are stil...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00G01N33/00C12Q1/02A61P31/00A61K31/295G01N33/53
CPCA01K2267/0387G01N2500/10G01N2333/445G01N33/56905A61P31/00A61P33/06Y02A50/30A61K39/015A61K2039/572G01N2333/70596
Inventor AKIRA, SHIZUOISHII, KENCOBAN, CEVAYIR
Owner OSAKA UNIV
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