Method for removal of viruses from blood by lectin affinity hemodialysis

Abstract

The present invention relates to a method for using lectins that bind to pathogens having high mannose surface glycoproteins or fragments thereof which contain high mannose glycoproteins, to remove them from infected blood or plasma in an extracorporeal setting. Accordingly, the present invention provides a method for reducing viral load in an individual comprising the steps of obtaining blood or plasma from the individual, passing the blood or plasma through a porous hollow fiber membrane wherein lectin molecules are immobilized within the porous exterior portion of the membrane, collecting pass-through blood or plasma and reinfusing the pass-through blood or plasma into the individual.

Description

[0001] This application is a continuation of U.S. patent application Ser. No. 10 / 760,810, filed Jan. 20, 2004, which claims the benefit under 35 USC §119(e) of U.S. Provisional Application No. 60 / 440,771, filed Jan. 17, 2003, the disclosures of which are incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to the field of therapeutic methodologies for treating viral infections. BACKGROUND OF THE INVENTION [0003] A large number of viruses have been described which are pathogenic for humans. Among these viruses are many for which neither drugs nor vaccines are available. In cases where drug treatments are available, the occurrence of resistant mutations and drug side effects often limit the effectiveness of therapy. Examples of such viruses include Hepatitis C and human immunodeficiency virus (HIV). [0004] HIV is the etiological agent of acquired immunodeficiency syndrome (AIDS). It infects selected cells of the immune system thereby compromisin...

AI Technical Summary

Benefits of technology

[0016] The present invention relates to a method for using lectins that bind to pathogens having high mannose glycoproteins or fragments thereof to remove them from infected blood or plasma in an extracorporeal setting. Accordingly, the present invention provides a method for reducing viral load in an individual comprising the steps of obtaining blood or plasma from the individual, passing the blood or plasma through a porous hollow fiber membrane wherein lectin molecules are immobilized within the porous exterior portion of the membrane, collecting pass-through blood or plasma and reinfusing the pass-through blood or plasma into the individual.

[0017] Passage of the blood through the hollow fibers having immobilized lectin causes the virions and fragments thereof which contain high mannose glycoproteins to bind to the lectins, thereby reducing the viral load in the effluent. In one embodiment, this invention uses lectins that bind viral envelope proteins of many subtypes of HIV types 1 and 2 and SIV. The method of the present invention reduces the number of virions in the blood and rapidly and effectively reduces the levels of viral surface proteins in infected blood which may be toxic. It will be apparent to those skilled in the art that the method will assist in the clearance of other infections, frequently occurring simultaneously with HIV-1, such as hepatitis C virus (HCV) (Fauci et al., 1998, supra).

[0018] Thus, an object of the invention is to provide a method for reducing the viral load in the blood of an individual infected with a virus. In one embodiment, virions or protein fragments thereof or combinations thereof are removed from the blood of an individual infected with a virus.

[0019] Another object of the present invention is to provide a method for reducing the viral load in the blood by extracorporeal circulation of blood through hollow fibers containing immobilized lectins having affinity for viral high mannose glycoproteins.

Problems solved by technology

In cases where drug treatments are available, the occurrence of resistant mutations and drug side effects often limit the effectiveness of therapy.

It infects selected cells of the immune system thereby compromising the infected individual's immune response.

The hallmark of AIDS is the gradual loss of CD4+ T cells, which ultimately leaves the immune system unable to defend against opportunistic infections.

Currently there is no cure for HIV infection.

While more than 16 drugs and drug combinations have been approved by the FDA for treating HIV infection, the emergence of drug resistant mutants and the presence of the untreatable virus reservoirs (e.g. in memory T cells) has limited their usefulness.

Unfortunately, no effective HIV vaccine has been forthcoming due, in part, to the rapid mutation of the HIV genome and the inaccessibility of immunogenic epitopes of viral proteins.

They do not directly remove HIV virus.

However, none of these treatments effectively remove both virus and viral proteins.

However, none of these chromatographic materials are selective for viruses and will clearly remove many other essential substances.

Thus they are not usefull for in vivo blood purification.

However, this strategy was inefficient as it required extracorporeal absorption of blood and did not provide for a mechanism to remove free HIV viral particles from the blood (Lopukhin et al., 1991, supra).

Accordingly, although lectins are known to bind viral envelope glycoproteins, no previous technologies have been developed using lectins to directly adsorb HIV or other enveloped viruses from the blood using in vivo dialysis or plasmapheresis.

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