Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

Abstract

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include antibody, antibody fragment, siRNA and vaccine compositions having or directed against a GRP78 polypeptide or an antigenic fragment of the polypeptide.

Description

[0001]This application claims the benefit of priority to the U.S. provisional patent application Ser. No. 61 / 239,026, filed Sep. 1, 2009, which is herein incorporated by reference in its entirety.[0002]This invention was made in part with U.S. Government support under NIH grant 011671 awarded by NIAID. The U.S. Government can have certain rights in the invention.BACKGROUND OF THE INVENTION [0003]This invention generally relates to compositions and methods for treating and preventing infectious diseases in a patient and, more particularly, relates to compositions and methods using antibodies, antibody fragments, small interfering RNAs or vaccines for treating and preventing opportunistic fungal diseases.[0004]About 180 of the 250,000 known fungal species are recognized to cause disease (mycosis) in man and animal. Some of fungi can establish an infection in all exposed subjects, e.g., the systemic pathogens Histoplasma capsulatum and Coccidioides immitis. Others, such as Candida, Ase...

AI Technical Summary

Benefits of technology

[0014]In another embodiment, the present invention provides methods of treating or preventing a fungal condition by administering to a subject having, or susceptible to having, a fungal condition a therapeutically effective amount of an antibody or antibody fragment thereof that specifically binds to a GRP78 polypeptide or a fragment thereof.

[0015]In another embodiment, the present invention provides methods of treating or preventing a fungal condition by administering to

Problems solved by technology

Fungi of the class Zygomycetes, order Mucorales, can cause Mucormycosis, a potentially deadly fungal infection in human.

Because the fungus is relatively resistant to AmB, high doses are required, which frequently cause nephrotoxicity and other adverse effects (Sugar, supra).

Also, in the absence of surgical removal of the infected focus (such as excision of the eye in subjects with rhinocerebral mucormycosis), antifungal therapy alone is rarely curative (Edwards, J.

Furthermore, ischemic necrosis of infected tissues as a result of fungal angioinvasion can prevent delivery of adequate levels of antifungal therapies, and is likely an important mechanism by which the fungus survives despite therapy with fungicidal agents.

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