Virus-like particles for the induction of autoantibodies

DETAILED DESCRIPTION The inventors have discovered compositions and methods of increasing the titers of antibodies to tolerogens (e.
g.
, self antigens and foreign antigens) over those titers routinely generated spontaneously or after conventional methods of vaccination.
In several embodiments, the break in B cell tolerance is accomplished by using a support or capsomeric structure having an ordered assembly of subunits or capsid proteins joined to at least one B cell epitope of a tolerogen, wherein the tolerogen is presented in a regular, repetitive array.
In some aspects of the invention, the tolerogen and the viral capsid protein are derived from different organisms, viruses, or infectious agents.
The support can be a bead, a lipid membrane, or a protein polymer.
The capsomeric structure can have icosohedral or helical symmetry.
In desirable compositions, however, the capsomeric structure is comprised of viral capsid proteins that self-assemble to form an organized structure referred to as "virus-like particle," or VLPs.
In some embodiments, the viral capsid proteins are hybrid molecules or are otherwise modified.
Thus, some embodiments are "chimeric virus-like particles (VLPs)" and others are "conjugated virus-like particles (VLPs)", wherein "chimeric VLPs" have a tolerogen joined to the viral capsid protein (or its homolog) by genetic engineering (e.
g.
, creation of a tolerogen/capsid protein fusion) and "conjugated VLPs" have a tolerogen joined to the viral capsid protein (or its homolog) by way of chemical, physical or other modification of the capsid protein or tolerogen or both (e.
g.
, biotin/streptavidin, biotin/avidin, other ligand/receptor sequences).
Thus, aspects of the invention include a composition comprising a support having an ordered assembly of subunits and at least one B cell epitope of a tolerogen joined to the support so as to form a tolerogen-presenting immunogen, wherein the tolerogen-presenting immunogen displays the tolerogen in a regular, repetitive array.
Other compositions of the invention comprise a capsomeric structure having a symmetrical assembly of capsid proteins and at least one B cell epitope of a tolerogen joined to the capsomeric structure so as to form a tolerogen presenting virus-like particle (VLP), wherein the tolerogen presenting VLP displays the tolerogen in an ordered, repetitive array