Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by interference with neuromuscular transmission by
autoantibodies against the
nicotinic acetylcholine receptor (AChR) on muscle. Previously, 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 and the dominant Lewis rat
T cell epitope (alpha-chain residues 100-116) of the AChR, respectively, are effective
vaccines that prevent EAMG in rats by inducing antiidiotypic/clonotypic
antibodies (Ab) and lowering levels of AChR Ab. These studies employed
keyhole limpet hemocyanin (KLH) as a carrier and complete
Freunds adjuvant (CFA). In advance of a clinical trial the present study tested the efficacy of RhCA 611-001 when combined with different adjuvants that are approved for use in humans. Adjuvants chosen for comparison were incomplete
Freunds adjuvant (IFA) and
aluminum hydroxide (
Alum). As a second goal we evaluated
diphtheria toxin (DT) as an alternative
carrier protein to KLH.
Alum was found to be an effective adjuvant, particularly when used with the
peptide conjugated to DT. This combination of carrier and adjuvant provided protection against EAMG comparable with that observed with CFA and KLH. Using
enzyme-linked
immunosorbent assays for Ab against RhCA 611-001, it was found that disease protection is qualitatively, but not quantitatively, related to the anti-
peptide Ab response. Our results demonstrate a
vaccine formulation that should be useful in the first soon-to-be-conducted clinical trials of
peptide vaccines to specifically correct aberrant T and B cell responses in an
autoimmune disease.