Clinical trials have been conducted with several different anti-nicotine vaccines that comprise nicotine-like haptens conjugated to different carriers, and an adjuvant that is most often an aluminum salt. For these vaccines, the putative mechanism of action is that they will induce anti-nicotine antibodies that bind nicotine in the periphery, thus reducing the amount of nicotine entering the brain, which should in turn reduce reward and help break the addiction cycle. Vaccines targeting nicotine are being developed as an alternative approach to treat nicotine dependence. These treatments are beneficial for promoting short-term abstinence but are only modestly effective over the long-term, with fewer than one-quarter of treated subjects remaining abstinent at the end of one year. Pharmacological treatments currently used for smoking cessation are most often nicotine replacement therapies (e.g., gums, patches) or prescription drugs that act within the central nervous systems to reduce nicotine reward and/or symptoms of withdrawal. While the vast majority of adult smokers wish to quit, approximately 80% of those who attempt to quit on their own will relapse within the first month of abstinence and less than 5% will remain abstinent at 6 months. Tobacco use is responsible for approximately six million deaths annually and poses a substantial burden on public health worldwide. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Benoit, KR, JM, HD and MM all hold shares or share options of Pfizer. There are no marketed products to declare. Pfizer is pursuing patents and product development on compounds that are mentioned in this paper. Co-authors YW, GM, and RG were employed by Peakdale Molecular Ltd at the time of these studies. With Pfizer at the time of these studies. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: No current external funding sources for this study.Ĭompeting interests: All authors were either under paid employment or consultancy agreement Received: ApAccepted: AugPublished: October 1, 2013Ĭopyright: © 2013 Pryde et al. Janda, The Scripps Research Institute, United States of America (2013) Selection of a Novel Anti-Nicotine Vaccine: Influence of Antigen Design on Antibody Function in Mice. While both Ab titer and affinity contributed to function, affinity was more sensitive to antigen differences.Ĭitation: Pryde DC, Jones LH, Gervais DP, Stead DR, Blakemore DC, Selby MD, et al. These results demonstrate that immune responses induced in mice by nicotine-conjugate antigens are greatly influenced by hapten design including site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. Linker also influenced Ab titer, affinity and function. Several haptens gave similarly high Ab titers, but among these, Ab affinity and hence function varied considerably. Conjugates made with different haptens resulted in various titers of anti-nicotine Ab.
#Haptens have immunogenicity but not reactivity series
A series of additional linkers varying in length, rigidity and polarity were used with a single hapten to generate additional DT-conjugates, which were also tested in mice. The resulting hapten conjugates were evaluated in a mouse model, using CpG (a TLR9 agonist) and aluminum hydroxide (Al(OH) 3) as adjuvants, whereby Ab titers, affinity and function were evaluated using a radiolabeled nicotine challenge model. In this study, we designed and synthesized a series of novel nicotine-like haptens which were all linked to diphtheria toxoid (DT) as carrier, but which differed in the site of attachment of linker to nicotine, the nature of linker used, and the handle used to attach the hapten to DT. Anti-nicotine vaccines tested previously in clinical studies had poor efficacy despite high Ab titer, and this may be due to inadequate function if Ab of low affinity were induced. Ab function depends on both the quantity (titer) and the quality (affinity) of the Ab. Anti-nicotine vaccines may aid smoking cessation via the induction of anti-nicotine antibodies (Ab) which reduce nicotine entering the brain, and hence the associated reward.
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