Abstract
Vaccination against self-antigens to avert pathological immunity to self - ‘negative vaccination’ - is the Holy Grail of autoimmune disease therapy. This approach depends on deletion or inactivation of pathogenic T cells, or induction of protective, ‘regulatory’ T cells. While effective in inbred rodent models, it is yet to be translated to humans. Reasons for this include its application only in end-stage disease, ignorance about antigen form, route of delivery and dose-schedule required for a bio-response, lack of meaningful and measurable bio-response markers, co-activation of pathogenic immunity and genetic heterogeneity.