TL neuro

December 20, 2012

Functional efficacy of an anti-methamphetamine vaccine

Filed under: Methamphetamine, Thermoregulation, Vaccines — mtaffe @ 9:31 am

An early study which attempted to generate active vaccination against methamphetamine (METH) found no significant differences between vaccinated and control rats in a locomotor response to METH (Byrnes-Blake et al. 2001), however the vaccine led to a monoclonal antibody which was effective as a passive vaccine in a range of pharmacological studies including pharmacokinetic, animal models of drug overdose, locomotor activity, self-administration, and drug discrimination (Byrnes-Blake et al. 2003; McMillan et al. 2002). Passive vaccines are considered to be less ideal because they require the infusion of large quantities of drug-specific antibodies which must be manufactured and stored for use. In many cases active vaccine can be manufactured more cheaply and the antibodies are then generated by the immune system. Typically, or perhaps ideally, the duration of protection for passive vaccination is not as long as with active vaccination. Thus there continues to be interest if determining if active vaccination can work.

Another group found that active vaccination with the same hapten published by Byrnes-Blake (2001), coupled to a “molecular adjuvant” with a tetanus toxin T-cell epitope in place of the traditional keyhole limpet hemocyanin (KLH), resulted in an intial increase in methamphetamine self-administration in rats, followed by a decrease to levels indistinguishable from controls over 15 sessions (Duryee et al. 2009). This enhances confidence that it would be possible to develop active vaccines against methamphetamine.

The following paper is now in press at Biological Psychiatry.

Miller ML, Moreno AY, Aarde SM, Creehan KM, Vandewater SA, Vaillancourt BD, Wright MJ Jr, Janda KD, Taffe MA. A Methamphetamine Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats.Biol Psychiatry. 2012 Oct 22. pii: S0006-3223(12)00803-7. doi: 10.1016/j.biopsych.2012.09.010. [Epub ahead of print] [PubMed][DOI]

VaccineTelem-Fig2In this paper we have shown that active vaccination can protect against the effects of METH. This figure is reproduced from the paper and the data show that METH causes an elevation of body temperature and an increase in wheel activity in the control animals vaccinated with the carrier protein (KLH). These effects are blocked in the animals vaccinated with the MH6-KLH conjugate vaccine. These data show the potential for active vaccination to oppose effects of methamphetamine.

Another paper from a competing group (Shen et al, 2012) appeared at nearly the same time as ours, demonstrating efficacy of active vaccination against METH stimulated locomotor activity in mice. It is to be hoped that these three successful demonstrations of efficacy of anti-METH vaccines will overcome the apparent failure of the early Byrnes-Blake et al (2001) finding and stimulate additional research.

This project was supported by NIH/NIDA grant R01 DA024705.

A NIDA generated brief animation video on the basic idea of anti-drug vaccination can be found in this post.
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Additional Reading:

Byrnes-Blake KA, Carroll FI, Abraham P, Owens SM. Generation of anti-(+)methamphetamine antibodies is not impeded by (+)methamphetamine administration during active immunization of rats. Int Immunopharmacol. 2001 Feb;1(2):329-38. [PubMed]

Duryee MJ, Bevins RA, Reichel CM, Murray JE, Dong Y, Thiele GM, Sanderson SD. Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines. Vaccine. 2009 May 14;27(22):2981-8. doi: 10.1016/j.vaccine.2009.02.105. Epub 2009 Mar 10. [PubMed]

Shen XY, Kosten TA, Lopez AY, Kinsey BM, Kosten TR, Orson FM. A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Depend. 2012 Sep 27. doi: 10.1016/j.drugalcdep.2012.09.007. [Epub ahead of print] [PubMed]

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1 Comment »

  1. […] In this new paper we follow up on our first finding that a anti-methamphetamine conjugate vaccine (referred to as the MH6-KLH conjugate) changes locomotor activity and body temperature responses to methamphetamine [Miller et al, 2013; blog post]. […]

    Pingback by Active vaccination against methamphetamine slows acquisition of self-administration | TL neuro — June 7, 2015 @ 7:01 pm


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