Research Plan PROJECT SUMMARY/ABSTRACT Four factors make this methamphetamine (MA) vaccine ready for clinical translation: 1. Our candidate vaccine has optimal adjuvant and antibody responses; 2. Our partnering Chinese manufacturer has Chinese FDA support for the vaccine IND and matching clinical study funds; 3. The PI has 15 years experience developing medications in China and a successful cocaine vaccine. We can accelerate MA vaccine development well beyond the 15 years needed for cocaine in the USA, because the manufacturer has Chinese government financial and FDA support and commercial incentives from the lack of approved treatments for MA. Our R01(DA023898) has identified an optimal carrier protein - Keyhole Limpet Hemocyanin (KLH), which is already approved for human use, and an approved Chinese squalene lipid adjuvant that is better than standard alum to optimize the anti-MA antibody response to vaccination. The optimal KLH-adjuvant vaccine combination will be determined within two years by correlating the quality and quantity of the induced antibodies with inhibition of MA locomotion and self-administration behavior in rats and primates. We then rapidly moved into cGMP synthesis, animal toxicology, CMC, IND filing and phase 1 and 2a clinical trials in years four/five. 4. Concurrently with this Chinese human vaccine, we plan to renew R01-DA023898 to develop a similar lipid adjuvant vaccine in collaboration with the Sabin Vaccine Institute, which is moving to Baylor in July 2011 and has a squalene adjuvant (Easai, E6020) with FDA approval. These two linked programs will have major practical impacts on MA's profound morbidity in the USA and China through collaborative vaccine development between American and Chinese investigators and manufacturers to produce a first and potentially a second generation vaccine quickly into clinical development in the USA and Asia.
MA vaccines will provide practical and cost effective treatment options, as cocaine and nicotine vaccines have already shown. These vaccines can be implemented beyond this project?s Phase 1 endpoints in Phase 2 and 3 FDA approval studies for community treatment and potentially prevention. The MA vaccines can have substantial impact on general medical practice and on reducing major risks for HIV transmission worldwide through treating dependence and potentially preventing abuse.
| Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A (2017) Sex differences in the acute locomotor response to methamphetamine in BALB/c mice. Behav Brain Res 327:94-97 |
| Ohia-Nwoko, O; Kosten, T A; Haile, C N (2016) Animal Models and the Development of Vaccines to Treat Substance Use Disorders. Int Rev Neurobiol 126:263-91 |
| Haile, Colin N; Kosten, Therese A; Shen, Xiaoyun Y et al. (2015) Altered methamphetamine place conditioning in mice vaccinated with a succinyl-methamphetamine-tetanus-toxoid vaccine. Am J Addict 24:748-55 |
| Orson, Frank M; Wang, Rongfu; Brimijoin, Stephen et al. (2014) The future potential for cocaine vaccines. Expert Opin Biol Ther 14:1271-83 |
| Kosten, Thomas; Domingo, Coreen; Orson, Frank et al. (2014) Vaccines against stimulants: cocaine and MA. Br J Clin Pharmacol 77:368-74 |
| Kosten, Therese A; Shen, Xiaoyun Y; Kinsey, Berma M et al. (2014) Attenuation of cocaine-induced locomotor activity in male and female mice by active immunization. Am J Addict 23:604-7 |
| Ramakrishnan, Muthu; Kinsey, Berma M; Singh, Rana A et al. (2014) Hapten optimization for cocaine vaccine with improved cocaine recognition. Chem Biol Drug Des 84:354-63 |
| Brimijoin, Stephen; Shen, Xiaoyun; Orson, Frank et al. (2013) Prospects, promise and problems on the road to effective vaccines and related therapies for substance abuse. Expert Rev Vaccines 12:323-32 |
| Orson, Frank M; Rossen, Roger D; Shen, Xiaoyun et al. (2013) Spontaneous development of IgM anti-cocaine antibodies in habitual cocaine users: effect on IgG antibody responses to a cocaine cholera toxin B conjugate vaccine. Am J Addict 22:169-74 |
| Shen, Xiaoyun Y; Kosten, Therese A; Lopez, Angel Y et al. (2013) A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Depend 129:41-8 |
Showing the most recent 10 out of 13 publications
