Cocaine Vaccines

Although cocaine abuse and addiction have a serious health and social impact, there are no FDA-approved drugs for cocaine treatment. The anticocaine conjugate vaccine provides an attractive opportunity for addiction treatment. Creative Biolabs is a world leader in the field of vaccines against drugs of abuse. With our extensive experience and advanced platform, we are therefore confident in offering the best development services for cocaine vaccines.

Background of Cocaine Vaccines

Cocaine abuse remains the main medical and social hazard in the United States. The Drug Abuse Warning Network (DAWN) reported that 40.3% of drug-related emergency department visits were attributed to cocaine. Despite the seriousness of this problem, current treatment options are limited to alleviating cocaine symptoms. Traditional methods for treating drug abuse have been to prepare small molecule receptor ligands or endogenous signal molecule mimetics to cause specific changes in the neural circuit, including dopaminergic, glutamatergic and GABAergic signaling. Disadvantages of these methods are the potential for abuse of the therapeutic agent itself and the high risk of side effects associated with altering neurotransmitter signaling. Because of these limitations, pharmacokinetic (PK) strategies have been developed that maintain the free concentration of drugs in the central nervous system (CNS) below the minimally effective threshold. Classic vaccination is an effective way to achieve this goal. The basic strategy uses a cocaine vaccine to induce the immune system to produce a specific resistance that binds to the drug in the bloodstream and prevents it from entering the brain. One of the most challenging aspects of this approach is that the optimization in hapten, adjuvant and carrier preparations are required to induce broadly effective and highly specific anti-cocaine antibodies in a wide patient population.

The Mechanism of Action of Cocaine Vaccines

Cocaine vaccines stimulate the immune system to produce antibodies. Anti-cocaine antibodies bind to cocaine molecules in the blood, forming drug-antibody complexes that are too large to cross the blood-brain barrier and enter the brain. If the vaccinated person produces enough antibodies to capture and maintain most of the cocaine molecules circulating in the blood, the drug will not produce excitatory or other psychoactive effects that enhance drug intake and addiction.

Vaccines designed for cocaine: under normal conditions, cocaine molecules (shown in gold) can easily enter the brain from the blood (above). After the cocaine injection, the vaccine stimulates the patient's immune system to produce cocaine antibodies (red) that attach to the drug molecules and prevent them from reaching the brain (below).

Fig 1 Vaccines designed for cocaine: under normal conditions, cocaine molecules (shown in gold) can easily enter the brain from the blood (above). After the cocaine injection, the vaccine stimulates the patient's immune system to produce cocaine antibodies (red) that attach to the drug molecules and prevent them from reaching the brain (below). (Whitten. 2010)

The Challenge of Cocaine Vaccines

Cocaine has a low molecular weight, they are too small to elicit an immune response by themselves, but they can become immunogenic by conjugation with a suitable carrier protein. In order to achieve higher antibody titers, it is necessary to use a full immunogen to periodically boost the dose, not just cocaine. Conjugation or ligation of the drug with the carrier protein is typically accomplished using 4-6 atomic spacers such as succinic acid. There are no rules to predict which linkers are most effective, nor do they systematically compare linkers, linker strategies, or hapten ratios. Future research may need to address these issues systematically. For the best vaccine design, another practical problem is the difficulty in determining the actual antibody affinity and concentration. Common ELISA methods for determining affinity and concentration can be inaccurate, and equilibrium dialysis has been used to solve some of these problems.

Isosterism is designed as a hapten for cocaine vaccines. In contrast to the efficacy of heroin vaccines, cocaine vaccine efficacy benefits from increased hapten stability by amide isosteric substitution.

Fig 2 Isosterism is designed as a hapten for cocaine vaccines. In contrast to the efficacy of heroin vaccines, cocaine vaccine efficacy benefits from increased hapten stability by amide isosteric substitution. (Bremer and Janda. 2017)

Creative Biolabs is a leader in the field of vaccine development and has focused on the vaccines against drugs of abuse for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.

References

  1. Whitten L. (2010). Cocaine Vaccine Helps Some Reduce Drug Abuse. Nida Notes, 23(3): 1-6.
  2. Kimishima A, et al. (2018). Efficient Syntheses of Cocaine Vaccines and Their in Vivo Evaluation. ACS Medicinal Chemistry Letters, 9(5): 411-416.
  3. Kosten T, et al. (2014). Vaccines against stimulants: cocaine and MA. British journal of clinical pharmacology, 77(2): 368-374.
  4. Bremer P T and Janda K D. (2017). Conjugate Vaccine Immunotherapy for Substance Use Disorder. Pharmacological Reviews, 69(3):298-315.

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