Development and characterization of a novel conjugated methamphetamine vaccine

• Published in: Vaccine 2022-09, Vol.40 (41), p.5882-5891
• Main Authors: Kamal Hossain, Md, Hassanzadeganroudsari, Majid, Feehan, Jack, Deraos, George, Nurgali, Kulmira, Matsoukas, John, Apostolopoulos, Vasso
• Format: Article
• Language: English
• Subjects: Addictions; Amphetamine; Amphetamine-Related Disorders - drug therapy; Amphetamine-Related Disorders - prevention & control; Amphetamines; Animal models; Animals; Antibodies; Antibody; Antigens; Chromatography; Clinical trials; Conjugation; Drug abuse; Fourier transforms; Glycine; Glycine - therapeutic use; Haptens; Humans; Immune system; Immunogenicity; Immunotherapy; Infrared spectroscopy; Liquid chromatography; Lysine; Lysine - therapeutic use; Mannan; Mannans - therapeutic use; Mass spectrometry; Mass spectroscopy; Methamphetamine; Mice; Mice, Inbred C57BL; Overdose; Oxidation; Peptides; Proteins; Public health; Research design; Scientific imaging; Substance use; Thin layer chromatography; Vaccine; Vaccine development; Vaccines; Vaccines, Conjugate
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2022.08.043

•Development of a novel METH conjugated vaccine system to be used for the treatment of METH addiction.•Mannan has been used as an immunogenic carrier for the first time for METH conjugated vaccine.•Each step of vaccine development has been characterized by various analytical methods and are useful for future research involving a similar platform.•The novel conjugated vaccine has been proved to be immunogenic in the pilot animal study.•The proposed METH conjugated vaccine system will be further characterized in METH animal models which will pave the way for human studies. Methamphetamine (METH) addiction is a major public health concern globally with limited management options. The development of a METH vaccine through hapten design has received significant attention as a promising platform for the potential treatment of METH addiction and overdose, however there is yet to be a successful candidate in human trials. Research design and methods: In this study, we developed a novel conjugated METH vaccine using oxidized mannan (a polymannose) as an immunogenic carrier. A METH hapten was synthesized by using amphetamine and conjugated to mannan with a (Lysine-Glycine-Lysine-Glycine-lysine-Glycine-Lysine-Glycine-Lysine-Glycine) (KG)5 peptide linker. The reaction between amphetamine and (KG)5, oxidation of mannan, and conjugation of amphetamine-(KG)5 with oxidized mannan were confirmed by color tests, Fourier-transform infrared spectroscopy, gas and liquid chromatography mass spectrometry, thin-layer chromatography, and ultraviolet spectrophotometer. Additionally, the ability of the vaccine to generate antibodies was confirmed in C57BL/6 mice. The successful development and characterization of the METH-mannan conjugate vaccine, provides a potential therapeutic intervention to curb METH substance use disorders. Each step of vaccine development was characterized to aid in future research on these vaccines, and the immunogenicity shown in the animal models supports future evaluation of the approach. Future studies of the conjugated METH vaccine should evaluate the efficacy in animal models of acute and chronic METH to pave the way for human studies.