Lead Inventor:
Denong Wang, M.D., Ph.D.;
Nicholas J. Turro, Ph.D.;
Jeffrey T. Koberstein, Ph.D.
Discovery of sugar moieties on anthrax spores for use in detection of spores, diagnosis of anthrax infection and the development of a next-generation vaccine
Conventional approaches to immunization often involve treatment using weakened microbes or purified surface proteins. However, the effectiveness of these approaches is limited by the ability of parasites to rapidly shuffle their surface proteins. Conversely, carbohydrates are both less mutable than proteins, and are only specific to parasites, as opposed to the host. This technology identifies the immunogenic sugar moieties of anthrax spores using their proprietary photo-activated glycan array. Anthrose-containing saccharides were found to be highly specific to anthrax spores (B. Anthracis), and present on the outer most surfaces of the spores. Identification of specific sugar-based moieties as antigenic determinants could be used for detection of anthrax spores, diagnosis of anthrax infection, and development of a novel next generation vaccine for anthrax.
Immunogenic sugar moieties enable rapid and accurate detection of anthrax to increase efficiency of current diagnostic methods and targeting the specific complex sugars present on anthrax spores promises to lead to more effective vaccines.
A novel photo-activated glycan array was developed and used to probe rabbit antibodies produced by immunization using anthrax spore antigens. The antibodies were found to bind best to anthrose monosaccharide and anthrose containing di-, tri-, and tetra-saccharides. The binding activities were found to correlate with the sizes of the oligosaccharide chains, with the anthrose monosaccharide being marginally reactive and the anthrose-containing tetrasaccharide showing the highest reactivity with anti-anthrax spore antibodies. Although, the terminal anthrose is the key sugar residue for antibody recognition, the a-L-rhamnopyranoyl trisaccharide internal chain also contributes to the formation of the antigenic determinants.
Applications:
-- Development of immunoassays for anthrax spore identification
-- Development of immunoassays for diagnosis of anthrax spore infection
-- Commercialization of photo-activated glycan array which can be used to study other pathogens
-- Anthrose and anthrose-containing oligosaccharides can be combined with a carrier protein to produce glycoconjugate for immunization/vaccination.
Advantages:
-- First identification of highly specific immunogenic sugar moieties of anthrax spores
-- Authors have developed, optimized, and characterized glycan-array technology
-- Versatility in array technology to study other pathogens
-- Sugars can be synthesized artificially
-- Sugars are pathogen specific and should exhibit no host cross-reaction
-- Increased efficiency in anthrax diagnostics
Issued US patent 8,658,573
Licensing Status: Available for licensing and sponsored research support
Related Publications:
Wang D. et al.
Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium. Proteomics, Vol. 7, Issue 2, Jan 2007, pp. 180-4.