Optimization of immunomodulatory properties of genetic vaccines

Patent Number: 7,390,619

Activation of T cells normally occurs by antigen presenting cells, of which the dendritic cell is the most potent.  T cells require signals from CD80 and CD86 on the antigen presenting cell in order to activate CD28, which is required for escape from anergy.  Since the T cell molecule CTLA-4 also binds CD80 and CD86, it is important to preferentially activate CD80 and CD86 instead of CTLA-4 for maximum T cell activation.

During genetic immunization, the antigen is delivered on a vector, however other molecules may also be delivered on the same vector, or on a different vector but administered to the same cells or location in vivo.  The current patent deals with ways of optimizing the CD80 gene that is added into the immunization vectors so as to obtain maximal T cell activity.

Specifically the patent covers ways of mutating CD80 with single or multiple nucleic acid substitutions and screening the mutant molecules for which one binds CD28 the best and binds CTLA-4 the weakest. 

View this patent on the USPTO website.