Dc-sign blockers and their use for preventing or treating viral infections

a technology of dcsign blockers and viral infections, which is applied in the field of dcsign blockers and their use for preventing or treating viral infections, can solve the problems of no dengue virus vaccine commercially available, hypovolemic shock fatality, etc., and achieve the effects of inhibiting the binding of hiv, inhibiting the binding, and inhibiting the binding

Inactive Publication Date: 2006-06-22
INST PASTEUR +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0040] an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of a viral effector molecule to a DC-SIGN receptor for the preparation of a medicament for preventing or treating a viral infection of a mammal, wherein the viral infection is mediated at least in part by the binding of the viral effector molecule to the DC-SIGN receptor of the mammal to be treated.
[0041] an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of a viral effector molecule to a DC-SIGN receptor for the preparation of a medicament for preventing or treating a viral infection of a mammal, wherein the viral infection is mediated at least in part by the binding of the viral effector molecule to the DC-SIGN receptor of the mammal to be treated.
[0042] an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of HIV or SIV to a DC-SIGN receptor present on dendritic cells of a human or a simian for the preparation of a medicament for preventing or treating an HIV or SIV infection of said human or said simian.
[0043] an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of HIV or SIV to a DC-SIGN receptor present on dendritic cells of a human or a simian for the preparation of a medicament for preventing or treating an HIV or SIV infection of a human or a simian.
[0044] an amount of a DC-SIGN modulator sufficient to substantially modulate the binding of ICAM-3 present on T cells of a mammal with DC-SIGN receptor present on dendritic cells of the mammal to prepare a drug for preventing or treating inflammation in said mammal caused by specific binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal.
[0045] an amount of a DC-SIGN blocker sufficient to substantially inhibit the binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal for the preparation of a medicament for preventing or treating inflammation in a mammal caused by specific binding of ICAM-3 present on T cells of the mammal with DC-SIGN receptor present on dendritic cells of the mammal. In a preferred embodiment the DC-SIGN blocker comprises a binding moiety of the Dengue virus E glycoprotein. In another preferred embodiment the mammal is a human.

Problems solved by technology

Although, in the majority of cases, the disease generally evolves favorably within a week, it may turn out to be fatal in the event of hypovolemic shock (DSS or dengue shock syndrome).
There is no commercially available vaccine against the dengue virus.
(Dengue and Dengue haemorrhagic fever (1997), 367-377), with unsatisfactory results.

Method used

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  • Dc-sign blockers and their use for preventing or treating viral infections
  • Dc-sign blockers and their use for preventing or treating viral infections
  • Dc-sign blockers and their use for preventing or treating viral infections

Examples

Experimental program
Comparison scheme
Effect test

example 1

Flaviviruses

[0177] The production and purification of DEN type-1 (DEN-1) virus strain FGA / NA d1d (GenBank accession number AF226686) (Duarte dos Santos et al. Virology, 274: 292, 2000) and West Nile (WN) virus strain IS-98-ST1 (GenBank accession number AF481864) (Mashimo et al., PNAS, 99: 11311, 2002) from mosquito Aedes pseudoscutellaris AP61 cell monolayers and virus titration on AP61 cells by focus immunodetection assay (FIA) were performed as previously described (Desprès et al., Virology, 196: 209, 1993). Yellow fever (YF) virus vaccine strain 17D-204 (STAMARIL, Pasteur Vaccins, Lot E113) (GenBank accession number: X07755) was propagated twice in African green monkey kidney VERO cell monolayers, purified in sucrose gradients and titrated on VERO cells. Infectivity titers were expressed as focus forming units (FFU).

[0178] It is noteworthy that FGA / NA d1d E glycoprotein has two N-linked glycosylation sites at positions Asn67 and Asn153. Both N-glycosylation sites of the DEN-1 g...

example 2

Human Mononuclear Cells

[0180] Human DCs from purified mononuclear cells, human monocytic cell line THP-1 (ATCC TIB 202) and DC-SIGN expressing cell clone, THP / DC-SIGN, were obtained from Ali Amara (Immunologie Virale) (Kwon et al., Immunity, 16: 135, 2002). Immature DC, THP-1 and THP / DC-SIGN cells were cultured in RPMI 1640 culture medium supplemented with 10% heat-inactivated fetal calf serum (FCS) (Eurobio, lot 160402), 2 mM L-glutamine and antibiotics Peni / Strepto.

[0181] DC were adhered to poly-L-lysine (Sigma)-coated glass Lab-tek chambers (Nalge Nunc International) (5×104 cells per cm2). THP-1 and THP / DC-SIGN cells were adhered to poly-L-lysine-treated glass Lab-tek chambers or polylysine-treated 12-well flasks (5×104 cells per cm2).

example 3

Virus Infections

[0182] Cells were washed once with RPMI 1640, incubated with highly purified virus in RPMI 1640 supplemented with 0.2% bovine serum albumine (BSA, pH 7.5) (Sigma) for 2 hrs at 37° C. and placed into fresh media supplemented with 2% FCS, 2 mM L-glutamine and antibiotics Peni / Strepto at 37° C. for 40 hrs.

[0183] The percentage of cells expressing viral antigen was determined using either DEN-1 virus-specific hyperimmune mouse ascites fluid (HMAF) 9801 (strain Hawaï), WN virus-specific HMAF 0801 (strain IS-98-ST1), or YF virus-specific HMAF 9803 (strain FNV) with dilution of 1:50, by indirect immunofluorescence as previously described (Desprès et al., J.Virol., 70: 4090, 1996).

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Abstract

The present invention relates to methods and compositions for preventing or treating diseases of a mammal, including viral infections, wherein at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor present on cells of the mammal to be treated. The invention also provides methods of identifying compositions, wherein the compositions are useful for treating mammalian diseases, including viral infections, for which at least one symptom of the disease is mediated at least in part by the specific binding of an effector molecule to a DC-SIGN receptor present on the cells that express the DC-SIGN receptor, belonging to the mammal to be treated. The invention further relates to compositions and methods for targeting subject molecules to cells that express the DC-SIGN receptor.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention relates to methods, uses and compositions for preventing or treating diseases of a mammal, wherein at least one symptom of the disease is mediated at least in part by the binding or interaction of an effector molecule to a DC-SIGN receptor of the mammal to be treated. The effector molecule may be a molecule of a foreign organism. The foreign organism may be a virus. [0003] The invention also relates to compositions, and to methods of identifying compositions, wherein the compositions are useful for treating mammalian diseases for which at least one symptom of the disease is mediated at least in part by the binding of an effector molecule to a DC-SIGN receptor of the mammal to be treated. [0004] The invention further relates to compositions and methods for targeting subject molecules to cells expressing DC-SIGN receptors, such as dendritic cells. These compositions and methods are based on targeting co...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K39/42A61K31/715A61K38/16A61P31/14A61P31/18C07K16/28G01N33/566G01N33/68
CPCA61K38/162A61K2039/505C07K16/2851C07K16/2896G01N33/566G01N33/6872G01N2333/70596G01N2500/00G01N2500/10A61P31/14A61P31/18Y02A50/30
Inventor AMARA, ALIARENZANA-SEISDEDOS, FERNANDODESPRES, PHILIPPEVIRELIZIER, JEAN-LOUIS
Owner INST PASTEUR
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