Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies

High avidity and long-lasting autoantibodies to a self-polypeptide (TNF-alp ha) were generated after parenteral vaccination of mice with low doses of v irus-like particle-based (VLP-based) vaccines that were constructed by link ing mouse TNF-alpha peptides to the surface of papillomavirus VLPs. High-ti ter autoantibodies were induced with or without coadministration of potent conventional adjuvants, but were enhanced by coadministration of CFA. Compa red with immunization with the fusion protein alone, attachment to VLPs inc reased autoantibody titers 1,000-fold. A comparison of Ab responses against the self (TNF-alpha) and foreign components of the fusion protein showed t hat VLP conjugation abrogated the ability of the humoral immune system to d istinguish between self and foreign. Similar levels of IgM were detected to self and foreign epitopes regardless of the assembly state of the antigen, suggesting that conjugation of self-peptides to VLPs promotes survival or expansion of mature autoreactive B cells. In a mouse model, vaccination wit h conjugated particles inhibited development of type II collagen-induced ar thritis. Together, these results suggest a potentially flexible method to e fficiently generate autoantibodies against specific self-proteins that medi ate arthritis and other diseases.