Work

Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

Year: 2013

Type: article

Abstract: Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm400228w

Authors: Xiaoqing Cai, Timothy Whitfield, Mark S. Hixon, Yanabel Grant, George F. Koob, Kim D. Janda

Institutions: Scripps Research Institute, Takeda (United States)

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute on Drug Abuse