Poster Presentation International Peptide Symposium 2023

Synthesis and in vivo evaluation of a synthetic anti-cocaine nanovaccine (#304)

Harrison Y.R. Madge 1 , Suzy Alexander 2 , Armira Azuar 1 , Jiahui Zhang 1 , Prashamsa Koirala 1 , Thomas H. Burne 2 , Istvan Toth 1 3 4 , Rachel J. Stephenson 1
  1. School of Chemistry and Molecular , The University of Queensland, Brisbane, Queensland, Australia
  2. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia
  3. Institute of Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  4. School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia

Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs, and unlike other commonly used substances of abuse has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anti-cocaine therapies, however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered the progress of translation of these anti-drug vaccines. This immunological strategy provides several advantages over traditionally investigated treatments, as the antibodies generated do not act on the brain and can therefore be used in combination with other treatments. Vaccination may also allow for an infrequent dosing regimen as antibodies persist for an extensive period following immunisation.

Previously reported cocaine vaccines have consisted of a small molecule drug-like hapten conjugated to a large immunogenic carrier protein and delivered with external adjuvant. The use of carrier proteins and adjuvant present a number of unfavourable properties on these formulations, including ineffective boosting, lack of pharmaceutical reproducibility and potential toxic effects from experimental adjuvants.

Here, we have designed and synthesised a self adjuvanting peptide-based anti-cocaine vaccine which is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunisation with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten antigen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.