MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS

Vaccination against nicotine is being studied as a potential treat-ment for nicotine dependence. Some of the limitations of vaccina-tion, such as variability in antibody titer and affinity, might be overcome by instead using passive immunization with nicotine-specific monoclonal antibodies. The effects of antibodies on nic-otine distribution to brain were studied using nicotine-specific monoclonal antibodies (NICmAbs) with Kd values ranging from 60 to 250 nM and a high-affinity polyclonal rabbit antiserum (Kd 1.6 nM). Pretreatment with NICmAbs substantially increased the bind-ing of nicotine in serum after a single nicotine dose, reduced the unbound nicotine concentration in serum, and reduced the distri-bution of nicotine to brain. Efficacy was directly related to antibody affinity for nicotine. Efficacy of the highest affinity NICmAb, NICmAb311, was dose-related, with the highest dose reducing nicotine distribution to brain by 78%. NICmAb311 decreased nic