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Chemokine receptors are expressed by many cells, including lymphoid cells, and function to mediate cell trafficking and localization. CC chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled receptor (GPCR) which regulates trafficking and effector functions of memory/effector T-lymphocytes, macrophages, and immature dendritic cells. Chemokine binding to CCR5 leads to cellular activation through pertussis toxin-sensitive heterotrimeric G proteins as well as G protein-independent signalling pathways.

This invention relates to a VAC-BAC shuttle vector system for the creation of recombinant poxviruses from DNA cloned in a bacterial artificial chromosome. A VAC-BAC is a bacterial artificial chromosome (BAC) containing a vaccinia virus genome (VAC) that can replicate in bacteria and produce infectious virus in mammalian cells.

This invention identifies a monoclonal antibody (4G10) against the chemokine receptor CXCR4 and is a mouse IgG1 antibody. CXCR4 has been identified as a co-receptor mediating entry of HIV-1 into T cells. Subsequently, CXCR4 has been implicated in normal physiological functions, including activation of B cells and B cell progenitors and guiding their migration into the bone marrow (via its ligand SDF-1). CXCR4 also functions in T cell progenitor migration and neural progenitor stem cell activation.

This invention claims Modified Vaccinia Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing Human Immunodeficiency Virus (HIV) env, gag, and pol genes, where the genes are isolated from Ugandan Clade D isolates, Kenyan Clade A isolates, and Tanzanian Clade C isolates. In a rhesus macaque SHIV model, DNA priming followed by a recombinant MVA (rMVA) booster controlled a highly pathogenic immunodeficiency challenge. Both the DNA and the rMVA components of the vaccine expressed multiple immunodeficiency virus proteins.

Available for licensing are methods of using Monoamine Oxidase Inhibitors (MAOIs) to prevent alpha-herpesvirus lytic infections, such as those caused by Herpes simplex virus (HSV-1 or HSV-2) and Varicella zoster virus (VZV), and to possibly prevent the periodic reactivation of these viruses from latency. MAOIs have been historically used to treat depression, hypertension, and related diseases. The invention describes how MAOIs can also inhibit LSD1, a histone/protein demethylase that is required for initiation of alpha-herpesvirus lytic infection.

The technology offered for licensing is in the field of vaccinia-based recombinant vaccines. In particular the invention relates to methods of stabilizing the recombinant virus, thus resulting in efficient production of the vaccine and efficient expression of the inserted gene. Stabilization of the recombinant virus is achieved by the insertion of the exogenous gene into an intergenic region (IGR) of the viral genome (i.e. Modified Vaccinia Ankara, MVA), where the IGR is flanked by open reading frames of conserved poxvirus genes.

One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells.

Investigators at the NIH have discovered a potential means for preventing or treating a herpes virus infection by inhibiting the activity of the host cell’s histone demethylases. When herpesviruses enter a cell, they are inactivated by cellular defense mechanisms that wrap the viral genome in repressive chromatin structures. In order for viral replication to progress, the host’s own histone demethylases are recruited to the viral genome to reverse this repression.

The present invention is related to a recombinant viral vector for vaccines.

Currently available poxvirus vectors for humans and other animals exhibit suboptimal expression of recombinant gene(s) and high expression of vector proteins which causes weak immunogenicity and high anti-vector immune response.

Herpes simplex viral infections, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), are exceptionally common worldwide. These viruses establish lifelong persistent infections with cycles of lytic reactivation to produce recurrent diseases including oral and genital lesions, herpetic keratitis/blindness, congenital-developmental syndromes, and viral encephalitis. Infection with HSV-2 increases the rate of human immunodeficiency virus (HIV) transmission in coinfected individuals. DNA replication inhibitors are typically used to treat herpesvirus infections.