Lead Inventors:
Denong Wang, Ph.D.,
Bernard F. Erlanger, Ph.D., Elvin A. Kabat, Ph.D.
Problem or Unmet Need:
Preventative medicine is widely accepted as a critical aspect of not only improving human health but also alleviating many pressures contributing to the rising cost of healthcare. Vaccinations represent a key component of preventative medicine. While the global vaccine market is very active, with revenues of almost $10 billion in 2005 and an estimated compound annual growth rate of 10.5% through 2012, there is continued demand for newer and more effective vaccines. Furthermore, as a number of vaccines are dependent upon T-cells, these types of vaccines are useless under conditions of T-cell deficiencies such as HIV or other infectious diseases.
Details of the Invention:
Alpha-1,6-dextran is a polysaccharide demonstrated to be a stable and non-toxic molecule through its use clinically as a blood expander. When injected into T-cell free mice, alpha-1,6-dextran was shown to elicit an enhanced IgA response, up to 50 fold higher than in normal mice. When coupled to or co-injected with another antigen, alpha-1,6-dextran can enhance the IgA response significantly over that of the co-antigen alone.
Applications:
As a conjugate, alpha-1,6-dextran can be used to develop improved vaccines. As the invention is capable of inducing an antibody response in a T-cell independent fashion, alpha-1,6-dextran is particularly useful for the development of vaccines for the treatment or prevention of AIDS and HIV as well as the development of other vaccines for immunocompromised individuals.
Advantages:
The invention provides a means for developing vaccines for patient populations that previously could not be treated (such as those with HIV). Alpha-1,6-dextran can also broaden the repertoire of responding B cells to a given antigen. And when coupled to a protein, alpha-1,6-dextran will have the benefit of inducing both a T-cell dependent and independent antibody response.
Patent Status: Issued Patent (
US 6,287,568)
Licensing Status: Available for Licensing and Sponsored Research Support
Publications:
1) Wang, D. and Kabat E. A. Carbohydrate Antigens (Polysaccharides), Chapter 9, In: Structure of Antigens, Volume Three, (ed. M.H.V.Van Regenmortal), pp.247-276, CRC Press, Boca Raton New York London Tokyo, 1996.
Wang, D., Wells, S. M., Stall, A. M. and Kabat, E. A.
Reaction of germinal centers in the T-cell-independent response to the bacterial polysaccharide a(1-->6)dextran. (1994) Proc. Natl. Acad. Sci. U.S.A. 91:2502-2506.
2) Wang, D., Hubbard, J. M. and Kabat, E. A.
Modeling Study of the Antibody Combining Sites to a(1-->6) dextrans: Predictions of the Conformational Contribution of VL-CDR3 and Jk Segments to Groove-type Combining Sites (1993) J. Biol. Chem., 168, 20584-20589.