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Method To Inactivate Viruses For Vaccine Development

Background:
The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of hydrophobic crosslinkers for vaccine development using enveloped viruses, such as HIV. 

Technology:
This invention describes a method of inactivating enveloped viruses by hydrophobic photoactivatable chemical crosslinking compounds and detergent treatment.  The inactivated viruses may be used as vaccines against the diseases caused by those viruses or as reagents in experimental procedures that require inactivated viral particles.  The compounds diffuse into the hydrophobic region of lipid bilayers of biological membranes, such as viral membranes.  When irradiated with UV, the compounds bind to proteins and lipids within the hydrophobic region resulting in crosslinks within the membrane and inactivation of the virus.  This crosslinked membrane is partially resistant to detergent solubilization.  Use of this crosslinker, followed by detergent treatment may result in preservation of the structural integrity and therefore immunogenicity of proteins on the exterior of the inactivated, detergent-treated virus.  The additional detergent step effectively eliminates the infectivity of any residual viral particles that are not adequately crosslinked.

Further R&D Needed:

• Interested collaborators are invited to provide statements for proposed in vitro or in vivo studies using various enveloped viruses
• Some examples of potential collaborative studies include, but are not limited to:
• Testing of the crosslinked, detergent-treated HIV-1 virus (or other enveloped viruses) for preservation of surface epitopes
• Analyzing the properties of the crosslinked and uncrosslinked HIV-1 virus (or other enveloped viruses) after detergent treatment
• Performing Northern blot analysis on the crosslinked and uncrosslinked virus to determine if the RNA has been crosslinked
• Studying the mechanism behind the UV activation of various azide-containing aromatic derivatives within lipid bilayers

• Mass spectrometry or other proteomic/lipidic analysis to identify which proteins and/or lipids are crosslinked to each other

• In vivo testing of inactivated enveloped viruses in animal models

• U.S. Provisional Application No. 61/025,424 filed 01 Feb 2008
• U.S. Provisional Application No. 61/088,294 filed 12 Aug 2008

• Novel method of inactivating enveloped viruses
• Ability to develop vaccines for HIV and other enveloped viruses

This opportunity is also listed under the following categories:

• Vaccines