DNA-Packaging Proteins May Hold Key to Lupus Vaccine

Zhang L and Dhatta SK. Prospects for a peptide vaccine for human lupus. International Journal of Clinical Rheumatology (2014) 9:229-232. doi: 10.2217/ijr.14.37

An investigational peptide vaccine may help normalize immune function in patients with systemic lupus erythematosus (SLE). It also may benefit  family members of SLE patientsand others at high risk for SLE, as predicted by genetic and other biomarkers, according to this editorial written by researchers from the Northwestern University Feinberg School of Medicine in Chicago..

The vaccine contains endogenous peptide epitopes in histones, the proteins that package DNA into nucleosomes.

Extensive in vivo studies of lupus-prone mice and in vitro studies of cells from human SLE patients have assessed its effects. The results suggest that it can counteract immune-system abnormalities by boosting regulatory mechanisms such as regulatory T cells (Tregs). A hallmark of SLE is inadequate activation of Tregs, which dampen the pathogenic response to nuclear autoantigens released by apoptotic cells.

Although global immunosuppression can control active SLE, it fails to achieve true immunological suppression, and risks toxic side effects, the authors point out. A targeted down-regulation of pathogenic autoimmune cells in SLE could follow such therapies, to “prevent recurrence and smoldering damage.”

Histone peptide epitopes meet the requirements for a vaccine, they note, because they:

•   Are non-toxic, derived from the body’s own proteins used to “educate” the immune system during development;
•   Suppress pathogenic autoantibody production and renal inflammation in vivo;
•   Can generate long-lasting, antigen-specific Tregs that suppress disease pathology;
•  Can induce cross-reactive, “tolerance spreading,” or linked tolerance to other pathogenic T- and B-cell autoepitopes, perhaps suppressing a broad spectrum of autoimmune response in SLE;
•   Can generate Tregs in SLE patients even in the presence of drugs hydroxychloroquine or steroids, or in lupus serum containing type I interferon (IFN)-inducing immune complexes.

“Overall, the fact that even healthy people can have regulatory mechanisms against nuclear autoantigens boosted by the histone peptides suggests the possibility of vaccinating apparently healthy people at risk for lupus with these peptides,” the authors state.

They add that the histone peptide epitopes "might have unique and as yet uncharacterized mechanisms for their potent immunoregulatory effects."