CC Chemokine Receptor 5 DNA, New Animal Models and Therapeutic Agents for HIV Infection

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.

4G10, a Monoclonal Antibody Against the Chemokine Receptor CXCR4, Raised Against a Synthetic Peptide of 38 Residues in Length Derived from the N-terminal Sequence of CXCR4

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.

Anti-Vaccinia Monoclonal Antibody

The current technology describes a monoclonal antibody that reacts with a vaccinia virus protein abundantly expressed under an early viral promoter after infection of cells. The antibody is useful for quantitating vaccinia virus infected cells and for studying the function of the protein to which it binds, which is known to be a double stranded RNA binding protein involved in resistance of the virus to interferons. This antibody is available for licensing through a biological materials license agreement.

A Shuttle Plasmid, Recombinant MVA/HIV1 Clinical Vaccine Constructs and a Mechanism for Enhanced Stability of Foreign Gene Inserts by Codon Alternation and for Insertion of the Foreign Gene Between Two Vaccinia Virus Essential Genes

Since the onset of the AIDS epidemic more than two decades ago, enormous efforts have been directed to making a vaccine that will protect against human immunodeficiency virus-1 (HIV); an effective vaccine is thought to require the induction of cellular and humoral responses. Vaccine candidates have included a variety of HIV immunogens delivered as DNA, attenuated poxviruses, adenoviruses, vesicular stomatitis virus, proteins, and various combinations thereof. The inventors' efforts to design an HIV vaccine have focused on modified vaccinia virus Ankara (MVA) as a vector.

HIV Monoclonal Antibodies

This technology describes several hybridomas that produce monoclonal antibodies (mAbs) useful in HIV research applications. The mAbs are specific for either gp41 or gp120. In particular, the hybridomas producing mAbs designated D19, D56, M12, T8 and T24 (all anti-gp120), and T32 and T33 (gp41 specific) were found to be of particular utility. Additional hybridomas expressing mAbs disclosed in the publications may also be available.

Biological/Research Material for H1N1 Influenza Virus Vaccine Research

Offered for licensing is a recombinant attenuated vaccinia virus, MVA, that expresses the haemagglutinin (HA) and nucleoprotein (NP) of influenza virus A/PR/8/34 (H1N1). The virus has been shown to stimulate protective immunity to influenza virus in mice.

The materials can be used for research purposes and in particular in the area of influenza virus vaccines.

The related publications listed below demonstrate the usefulness of this biological material in influenza virus vaccine research.

Method of Producing Immortalized Primary Human Keratinocytes for HPV Investigation, Testing of Therapeutics, and Skin Graft Generation

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.