Details

Autor(en) / Beteiligte

• Stevens, Misty W.
• Rüedi-Bettschen, Daniela
• Gunnell, Melinda G.
• Tawney, Rachel
• West, C. Michael
• Owens, S. Michael

Titel

Antibody production and pharmacokinetics of METH in rats following vaccination with the METH vaccine, IXT-v100, adjuvanted with GLA-SE

Ist Teil von

• Drug and alcohol dependence, 2019-11, Vol.204, p.107484-107484, Article 107484

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Applied Social Sciences Index & Abstracts (ASSIA)

Beschreibungen/Notizen

• •Vaccination with IXT-v100 elicits high affinity anti-METH antibodies in rats.•METH pharmacokinetics are significantly altered in vaccinated animals.•Vaccine with hapten density of 40 mol/mol identified as target for manufacturing. Methamphetamine use disorder continues to be inadequately treated, but improvements are being made in the field of immunotherapeutics, including vaccines, which could provide new options for treatment. Cocaine and nicotine vaccines have been tested clinically, but have yet to elicit the necessary antibody concentrations required to be effective. Methamphetamine vaccines have been tested in multiple nonclinical models and appear promising. Improved adjuvants have the potential to further stimulate the immune system to reach effective levels of antibodies. Previously, the methamphetamine vaccine IXT-v100 was administered with GLA-SE, a toll-like receptor 4 agonist, in mice to produce higher levels of antibodies than when it was administered with two other widely used adjuvants, Alhydrogel and Sigma Adjuvant System. The purpose of this research was to evaluate IXT-v100, given in combination with the adjuvant GLA-SE, to determine its efficacy in antagonizing methamphetamine disposition in a rat pharmacokinetic study. Additional rat studies were conducted to compare the ability of IXT-v100 manufactured with greater hapten densities to elicit higher antibody levels. As expected based on prior studies with anti-methamphetamine monoclonal antibodies, the antibodies resulting from vaccination with IXT-v100 altered methamphetamine pharmacokinetics by increasing serum concentrations and extending the half-life. Furthermore, intentional variations in the ratio of components during manufacturing led to production of vaccines with higher hapten densities. The higher hapten densities resulted in production of antibodies that maintained the ability to bind methamphetamine with high affinity. The results support continued development of IXT-v100 for the treatment of methamphetamine use disorder.