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Nucleotide-based Carbohydrate Vaccines

技术优势: Powerful method to produce vaccineExhaustive antigen epitope spaceHigh throughput

详细技术说明: The invention relates to a method of directedevolution of a large library of carbohydrate-oligonucleotide conjugates, andthen a therapeutically-useful monoclonal antibody is used to bind those membersof the library which best resemble its native epitope. Through amplification ordiversification of the best binders from the first library, the best epitopemimics are selected from subsequent library generations to provide improvedbinders. The carbohydrate-oligonucleotide conjugates obtained from the processpresent carbohydrates in an environment similar to that of the natural epitope.Such a compound, when formulated with the appropriate immunogenic carrier andadjuvant, would constitute a vaccine.

*Abstract: Certain monoclonal antibodies have therapeutic potentialagainst a particular disease, even though similar antibodies seldom or neverarise during disease progression in most humans. In such cases, a "reverseimmunology" approach would be desirable, in which an immunogen is designedwhich structurally mimics the epitope of the therapeutically useful monoclonalantibody. Immunization with this epitope mimic would then elicit an antibodyresponse mimicking the monoclonal antibody.
The success of this strategy depends on theextent to which one can design a molecule that is a good structural andconformational mimic of the native epitope. Carbohydrates are necessary epitopescomponent for antibody binding. Carbohydrates are flexible and may exhibitdifferent conformational profiles when attached to structures other than thosepresent in the actual target protein. Good vaccine can be produced, if thetarget protein epitope can be faithfully mimicked using backbone ofcarbohydrates embedded in the oligonucleotide framework.

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