The role of adjuvants in the efficacy of a peptide vaccine for myasthenia gravis

Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) M G, are caused by interference with neuromuscular transmission by autoantibo dies against the nicotinic acetylcholine receptor (AChR) on muscle. Previou sly, we have shown that two peptides, denoted RhCA 67-16 and RhCA 611-001, designed to be complementary in structure to the main immunogenic region an d the dominant Lewis rat T cell epitope (cu-chain residues 100-116) of the AChR, respectively, are effective vaccines that prevent EAMG in rats by ind ucing anti-idiotypic/clonotypic antibodies (Ab) and lowering levels of AChR Ab. These studies employed keyhole limpet hemocyanin (KLH) as a carrier an d complete Freunds adjuvant (CFA). In advance of a clinical trial the prese nt study tested the efficacy of RhCA 611-001 when combined with different a djuvants that are approved for use in humans. Adjuvants chosen for comparis on were incomplete freunds adjuvant (IFA) and aluminum hydroxide (Alum), As a second goat we evaluated diphtheria toxin (DT) as an alternative carrier protein to KLH. Alum was found to be an effective adjuvant, particularly w hen used with the peptide conjugated to UT. This combination of carrier and adjuvant provided protection against EAMG comparable with that observed wi th CFA and KLH, Using enzyme-linked immunosorbent assays for Ab against RhC A 611-001, it was found that disease protection is qualitatively, but not q uantitatively, related to the anti-peptide Ab response. Our results demonst rate a vaccine formulation that should be useful in the first soon-to-be-co nducted clinical trials of peptide vaccines to specifically correct aberran t T and B cell responses in an autoimmune disease.