Methamphetamine Vaccines

Current methods to reduce methamphetamine addiction and relapse are ineffective in mitigating this growing global epidemic. Developing a vaccine for methamphetamine will provide a complementary strategy for existing therapies, but this has proven challenging. 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 methamphetamine vaccines.

Background of Methamphetamine Vaccines

Methamphetamine Vaccines– Creative Biolabs

Methamphetamine (MA) is a highly addictive stimulant. Over the past two decades, methamphetamine abuse has grown at an alarming rate in the United States and is spreading in Southeast Asia and East Asia. Currently, there are no drugs approved by the FDA for the treatment of MA addiction. The high addiction of MA is associated with the production and release of various neurotransmitters in the brain, including dopamine (DA), norepinephrine (NE), serotonin (5-HT), histamine, and gamma-aminobutyric acid (GABA). Because of these multiple effects, MA is less likely than other drugs of abuse to be effectively treated with specific pharmacological antagonists or alternative agonists. An increasingly attractive approach to drug addiction treatment is to use a conjugate drug vaccine to induce specific antibodies to block drug abuse. Conjugate vaccines developed for cocaine and nicotine have been developed into clinical trials. The data from these trials suggest that many patients may not produce adequate antibody responses, but the use of drugs is reduced and the rate of abstinence can be good. Anti-MA vaccines may also be a viable treatment for MA addiction. There are several options in vaccine construction, including hapten design, selection of carrier proteins, chemical localization of linkers between target antigens and carrier proteins, and selection of adjuvants.

The Mechanism of Action of Methamphetamine Vaccines

As a small molecule, MA cannot be recognized by the immune system alone. It needs to be conjugated to an immunogenic carrier to be efficiently processed and recognized by leukocytes, and ultimately to produce a sustained antibody response. In theory, anti-MA vaccines produce antibodies that bind to MA, so when MA enters the bloodstream subsequently, these antibodies will bind to it and form an antibody-MA complex in the circulatory system. This complex is too large to easily cross the blood-brain barrier, thus reducing the rate or amount of MA entering the brain. The antibody-bound drug will then be slowly released from antibody binding in the equilibrium state as residual-free drug to be metabolized and eliminated. The decrease in the rate or amount of MA entry into the brain should diminish its behavioral effects, including its ability to receive rewards.

The mechanism of action of anti-drug antibodies. The combination of the IgG antibody produced by the vaccine with the target drug in the blood results in a decrease in the concentration of the drug in tissues and organs, most importantly the brain, thereby reducing the pharmacodynamic effect of the drug.

Fig 2 The mechanism of action of anti-drug antibodies. The combination of the IgG antibody produced by the vaccine with the target drug in the blood results in a decrease in the concentration of the drug in tissues and organs, most importantly the brain, thereby reducing the pharmacodynamic effect of the drug. (Bremer and Janda. 2017)

The Challenge of Methamphetamine Vaccines

Vaccines for nicotine and cocaine have reached clinical trials, but vaccine research for the treatment of MA is still in its infancy. In order to effectively bind MA, the vaccine must elicit a high concentration of high-affinity MA-specific antibodies. The affinity and specificity of the antibodies produced are primarily dependent on the effective hapten, which is a major challenge due to the small size of the drug and its limited chemical epitope. A number of studies have reported a series of MA haptens, but there are many important methodological variabilities in the drug abuse field, which makes the hapten design itself defective. These factors include carrier proteins, formulation vaccination schedules, adjuvants and analytical methods. Therefore, we sought to further optimize the MA hapten, but more directly compared to other successful haptens.

The Design of Methamphetamine Vaccines

Design and manufacture of drug-conjugated vaccines. Using synthetic chemistry, the linker is attached to a target drug that has a cross-linking function at the end of the linker. Activation of this function couples the drug hapten to the carrier protein to produce an immunoconjugate. The drug immunoconjugate is formulated with a depot and an immunostimulating adjuvant to produce a complete vaccine. Multiple immunizations of the vaccine induce the immune system to produce drug-neutralizing IgG antibodies. The specific operation process is as follows:

Design and manufacture of drug-conjugated vaccines.

Fig 3 Design and manufacture of drug-conjugated vaccines. (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. Collins K C, et al. (2016). Methamphetamine Vaccines: Improvement through Hapten Design. Journal of Medicinal Chemistry, 28;59(8):3878-85.
  2. Shen X Y, et al. (2013). A VACCINE AGAINST METHAMPHETAMINE ATTENUATES ITS BEHAVIORAL EFFECTS IN MICE. Drug & Alcohol Dependence, 129(1-2):41-48.
  3. 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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