Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines.
Vaccines to methamphetamine (meth) were designed by covalently attaching a meth hapten (METH) to peptide constructs that contained a conformationally biased, response-selective molecular adjuvant, YSFKPMPLaR (EP54). Rats immunized with EP54-containing meth vaccines generated serum antibody titers to authentic meth, an immune outcome that altered meth self-administration. Immunization increased meth self-administration suggesting pharmacokinetic antagonism. The ability of immune sera to bind a METH-modified target protein dramatically decreased during and shortly after the meth self-administration assay, suggesting effective sequestration of free meth. However, the binding ability of immune sera to the METH-modified target protein was recovered 34 days after meth-free clearance time.
Experimental Immunology Laboratory, Omaha Veterans Administration Medical Center, Research Services 151, Omaha, NE 68105, USA.
Michael J
MJ
Duryee
Rick A
RA
Bevins
Carmela M
CM
Reichel
Jennifer E
JE
Murray
Yuxiang
Y
Dong
Geoffrey M
GM
Thiele
Sam D
SD
Sanderson
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D019969:Amphetamine-Related Disorders / Q000276:immunology* / Q000517:prevention & control*; D000818:Animals; D000906:Antibodies / Q000097:blood; D015936:Complement C5a / Q000008:administration & dosage / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D008297:Male; D008694:Methamphetamine / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012646:Self Administration; D019966:Substance-Related Disorders / Q000276:immunology* / Q000517:prevention & control*; D022223:Vaccines, Subunit / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D006241:Haptens; D010446:Peptide Fragments; D022223:Vaccines, Subunit; C105322:complement C5a, (65-74), Tyr(65)-Phe(67)-Pro(69,71)-Ala(73)-; D008694:Methamphetamine; D015936:Complement C5a