A methamphetamine vaccine using short monoamine and diamine peptide linkers and poly-mannose
. 2024 Sep 19:113:117930.
doi: 10.1016/j.bmc.2024.117930.
Online ahead of print.
Affiliations
Item in Clipboard
Bioorg Med Chem.
.
Abstract
Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by 1H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, 1H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster.
Keywords:
Diamine linker; Drug addiction; Hapten; Linker; Mannan; Methamphetamine; Monoamine linker; Oxidized mannan; Poly-mannose; Substance use disorder; Vaccine.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Fonte original PubMed