Suppression of Cocaine-Evoked Hyperactivity by Self-Adjuvanting and Multivalent Peptide Nanofiber Vaccines

• Published in: ACS chemical neuroscience 2016-05, Vol.7 (5), p.546-552
• Main Authors: Rudra, Jai S, Ding, Ye, Neelakantan, Harshini, Ding, Chunyong, Appavu, Rajagopal, Stutz, Sonja, Snook, Joshua D, Chen, Haiying, Cunningham, Kathryn A, Zhou, Jia
• Format: Article
• Language: English
• Subjects: Adjuvants, Pharmaceutic; Animals; Cocaine - antagonists & inhibitors; Cocaine - toxicity; Dose-Response Relationship, Drug; Hyperkinesis - chemically induced; Hyperkinesis - prevention & control; Locomotion - drug effects; Locomotion - physiology; Male; Mice; Mice, Inbred C57BL; Nanofibers - administration & dosage; Nanofibers - chemistry; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - chemistry
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.5b00345

The development of anti-cocaine vaccines that counteract the rewarding effects of the drug are currently being investigated as adjunct therapies for prevention of relapse in abstinent users. However, cocaine is weakly immunogenic and requires conjugation to carrier proteins and coadministration with strong adjuvants, which carry the risk of local reactogenicity and systemic toxicity. Here we report synthetic and multivalent self-assembling peptide nanofibers as adjuvant-free carriers for cocaine vaccines. A novel cocaine hapten modified at the P3 site was conjugated to the N-terminus of an amphipathic self-assembling domain KFE8. In aqueous buffers the cocaine-KFE8 conjugate assembled into β-sheet rich nanofibers, which raised anti-cocaine antibodies without the need for added adjuvants in mice. Vaccinated mice were treated with cocaine and a significant negative correlation was observed between antibody levels and cocaine-evoked hyperactivity. These totally synthetic and multivalent nanofibers with well-defined chemical composition represent the first generation of adjuvant-free cocaine vaccines.