The future potential for cocaine vaccines

Abstract

Introduction: Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine's pharmacodynamic effects.

Areas covered: This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness.

Expert opinion: Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes.

Keywords: addiction; adjuvant; antibody; butyrylcholinesterase; cocaine; gene therapy; hydrolase; vaccine.

Figure 1. Individual responses in groups of HIS-mice engrafted with single-donor stem cells

In this experiment, actively immunized groups of HIS-mice prepared from a single donor’s stem cells were vaccinated with 100 µg of succinylnorcocaine conjugated to tetanus toxoid (TT-SNC) with alum adjuvant at the beginning of week 1 with or without supplemental active cytokines (or cytokine control). Animals were boosted with the same vaccine conditions at week 3, and serum from each animal was collected at week 6 and tested by ELISA for anticocaine IgG antibody. The individual results are shown for each vaccine condition, expressed as the percent response compared with the standard condition group average (± standard deviation) defined as 100%.

Figure 2. Group responses of HIS-mice engrafted with different donor stem cells

In this experiment, actively immunized groups of HIS-mice prepared from different donors were vaccinated with 100 µg of TT-SNC with alum adjuvant at the beginning of week 1 and a booster dose of the same vaccine at week 3. Serum from each animal was collected at week 6 and pooled serum from each group was tested by ELISA for anticocaine IgG antibody. The group results are shown for each vaccine condition, expressed as the percent response compared to the donor 1 response arbitrarily defined as 100%. HIS-mice: Humanized immune system mice.