The role of adjuvants in the efficacy of a peptide vaccine for myasthenia gravis.
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.
McAnally
J L
JL
Department of Physiology and Biophysics and the Center for Neuroimmunology, University of Alabama at Birmingham, 35294, USA.
Xu
L
L
Villain
M
M
Blalock
J E
JE
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000276:immunology*; D004167:Diphtheria Toxin; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant; D006433:Hemocyanins; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D004167:Diphtheria Toxin; D004337:Drug Carriers; D010455:Peptides; D011978:Receptors, Nicotinic; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide; D005620:Freund's Adjuvant; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin