Harnessing the autoimmune response

Molecular mimicry, structural similarity between viral proteins and host molecules, is thought to explain the genesis of self-specific antibodies in autoimmune disease.

Here, Chackerian and coworkers propose a means to turn this pathological response to clinical advantage. The same group previously showed that one of the major capsid proteins of bovine papillomavirus can assemble spontaneously, even without other viral components, to form a population of viruslike particles (VLPs).

They have now developed a versatile technique by which peptides can be conjugated to VLPs, a form in which even normally nonimmunogenic self epitopes can elicit high titers of specific antibodies.

Vaccination of mice with VLP-conjugated TNF-a peptides yields IgGs that inhibit this cytokine and can block or delay the onset of experimentally induced arthritis — a disease process that is driven by high levels of TNF-a. This robust immune response, as compared with that seen in control vaccinations with unconjugated TNF-a peptides, seems to reflect relatively late events in the activation of self-specific B cells.

IgM titers are not dramatically different when animals are exposed to the epitope in either conjugated or unconjugated form, but at some point during or after their commitment to IgG production, mature B cells become strongly influenced by the structural context of the epitope.

Presumably, VLP conjugation could be used to generate neutralizing antibodies to, and provide long-term suppression of, a variety of self or foreign molecules.