Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates.

摘要: Abstract Anti-nicotine vaccines aim to prevent nicotine entering the brain, and thus reduce or eliminate reward that drives addiction. Those tested in humans date have failed improve quit rates over placebo, possibly because antibody (Ab) responses were insufficient sequester enough blood majority of subjects. We previously shown mice carrier, hapten linker used conjugate antigen each influence function (nicotine-binding capacity) Ab induced. Herein we evaluated immunogenicity 27 lots NIC7–CRM, a 5-aminoethoxy-nicotine (Hapten 7) mutant nontoxic form diphtheria toxin (CRM197), differed three attributes, namely load (number haptens conjugated molecule CRM197), degree aggregation presence adducts (small molecules attached CRM197 via covalent bond during conjugation process). A range functional (reduced brain immunized animals relative non-immunized controls) obtained with different conjugates, which adjuvanted aluminum hydroxide CpG TLR9 agonist. Trends for better conjugates having 11 18, low level high molecular mass species (HMMS) (i.e., not aggregated) more limited testing cynomolgus monkeys confirmed these results. Thus load, are key attributes can induced by NIC7–CRM.