Press Releases:

Sept. 30, 2001 - Development of effective HIV-1 vaccines is one of the primary goals of AIDS research. Despite progress in prevention and powerful drug combinations that reduce viral load, the epidemic continues to spread. A pandemic now exists in Sub-Saharan Africa and new fronts are opening in Asia, areas that can least afford the current drug costs and that lack the appropriate infrastructure for drug delivery and monitoring. The best hope for eradication of this virus is the development of safe and effective vaccines (McMichael, A.J., et al. Nat. Med. 5:612-4, 1999).

It now seems clear that cytotoxic T lymphocytes (CTL) play a key role in an effective immune response against HIV-1 (Walker, B.D., et al. Nature 407:313-4, 2000) in some individuals with non-progressive disease. However, for the majority of others with chronic progressive disease, CTL responses to the natural infection are inadequate. Despite a robust CTL response, essentially all patients progress to AIDS. Thus, effective vaccines must do more than the natural infection (Berzofsky, J.A., et al. Immunol Rev 170: 151-72, 1999). Sequence modification of viral epitopes or "epitope enhancement" can increase the magnitude of the immune response. Almost without exception, these altered peptide ligands of a defined viral epitope have been limited to a few generated by single amino acid substitutions in a peptide sequence at contact positions thought to be relevant for MHC and TCR binding.

In response to need for safe and effective HIV-1 vaccines a major overall goal of the Vaccine Development Program at Mixture Sciences, Inc. (MSI) is to identify peptides for the design of prophylactic or therapeutic vaccines for HIV infection. The development at MSI of proprietary, very large synthetic combinatorial peptide libraries offers an important opportunity to identify highly immunogenic peptide analogues of T cell epitopes of HIV antigens. By harnessing the degeneracy of T cell recognition and the use of these novel combinatorial peptide libraries highly immunogenic "superagonists" mimic T cell ligands, some with little sequence homology to the natural epitopes, can be identified. These peptide mimics can ultimately be used in the design of an effective therapeutic HIV-1 vaccine.

Recently the National Institutes of Health awarded a Phase I SBIR totaling $600,000 to MSI for the project titled "Mimic Peptides of HIV-1 Epitopes as Vaccines." This grant will fund the identification of optimized immunogenic peptide mimics of 3 HIV Gag epitopes and one Vpr epitope as a prototype vaccine for HLA-A2.1 individuals. Polyclonal human CD8+ CTL lines specific for the well-characterized, immunodominant HLA-A2-restricted epitopes of the HIV gag protein and the Vpr protein will be used to scan MSI's combinatorial libraries for immunogenic peptide mimics. MSI will also generate evidence that these peptide mimics provoke good CTL responses in vivo in an HLA-A2.1 transgenic mouse model and verify their immunogenicity in humans by ex vivo priming of naive CD8 T cells as well as identify spontaneous reactivities to these in patients categorized as non-progressors or slow progressors.

The prototype studies conducted are a critical step towards the development of effective HIV-1 vaccines. These studies will be performed collaboratively with Drs. Kan-Mitchell and Crane of Wayne State University. Dr. Crane is Director of the HIV/AIDS Clinic, which follows a total of 1,500 HIV-infected patients with 2,000 clinic visits a month.

Mixture Sciences, Inc., a privately-held biotechnology company, specializes in biomedical research and drug discovery. We use a combination of proprietary and in-licensed technologies for the discovery of therapeutic and diagnostic candidates for the treatment of HIV/AIDS, cancer, diabetes, Multiple Sclerosis, and infectious diseases, including Lyme Disease. Our technologies have been validated and used by members of the academic and corporate community over the past decade.

Our success comes from being a worldwide leader in the use of mixture-based chemical libraries. Our unique position allows us to provide our collaborators exceptional technologies and expertise. Mixture Sciences, Inc. is committed to developing, improving, patenting and in-licensing new technologies in order to provide our collaborators with the most cost efficient methods for identifying ligands.