Аннотация:
One of the new directions of the nicotine addiction treatment are vaccination and use of monoclonal antibodies. Bovine serum albumin conjugated vaccines have been developed using 6-amino-benzamide nicotinic hapten, adenovirus and other particles. A vaccine based on 6-carboxymethylureido (+/-)-nicotine (CMUNic) coupled to keyhole limpet hemocyanin (KLH) showed antibody titers above 1:10,000 in the experiment, with antibody binding not inhibited by any of the nicotine metabolites. The affinity was 2.4 ± 1.6 x 10 (7) M-1, and the binding capacity was 1.3 ± 0.7 x 10 (-6) M, which corresponds to 0.1 ± 0.05 mg / ml IgG per milliliter of serum. Plasma nicotine binding was increased in the CMUNic-KLH group (83.4 ± 6.8% and 16.4 ± 14.2% in the control group). The HexonAM1 anti-nicotine vaccine based on the adenovirus protein resulted in high serum antibody titers: 1.1×10(6)±7.6×10(4), which was sufficient to suppress the behavior induced by nicotine administration. Vaccines based on nanoparticles have shown good results in the experiment (NanoNiccine, NanoNicVac). The effectiveness of vaccination was increased by the addition of the Toll-like receptor (TLR). The use of monoclonal antibodies (ATI-1013) reduced the level of nicotine in the brain of rats by 95%. ATI-1013 had high affinity and selectivity for nicotine; had a very long half-life in rodent models; dose-dependent decrease in the distribution of nicotine in the brain; significantly reduced the reinforcing effects of nicotine in the self-administration model; were safe. In clinical trials in humans, it has not yet been possible to achieve stable results.
Studies of vaccine and monoclonal antibodies therapy have shown the promise of this direction, first of all, to prevent relapses of tobacco and nicotine consumption. Good results of abstinence have been obtained in animal models, but while there is no completed development of effective immunotherapies for the treatment of nicotine dependence in humans. Further research is required to improve the effectiveness of these therapies.
Ключевые слова:
vaccination, nicotine addiction, antibodies to nicotine, monoclonal antibodies to nicotine, vaccines based on nanoparticles